Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure tre...Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.展开更多
BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles ...BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling.Macrophages polarize to two distinct phenotypes:M1 and M2,and such plasticity in phenotypes provide macrophages various biological functions.AIM To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.METHODS DCM mouse models were established and randomly divided into DM,atorvastatin,and metformin groups.C57BL/6 mice were used as the control.Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues.The expression of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),M1 macrophages(iNOS^(+)),and M2 macrophages(CD206^(+))were demonstrated by immunohistochemistry and immunofluorescence staining.The levels of TGF-β1,IL-1β,and TNF-αwere detected by ELISA and real-time quantitative polymerase chain reaction.Malondialdehyde(MDA)concentrations and superoxide dismutase(SOD)activities were also measured.RESULTS Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardialfibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment.Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin;lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium;decreased the concentration of MDAand increased SOD activity in myocardium of db/db mice;inhibited M1 macrophages;and promoted M2macrophages.CONCLUSION Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with theantioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulatingmacrophage polarization.展开更多
Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myo...Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myocardial fibrosis remains unexplored.The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts.Methods Primary rat adult fibroblasts were isolated,cultured,and randomly allocated into 4 groups:control group,transforming growth factor beta1(TGFβ1)stimulation group,liraglutide group,and TGFβ1+liraglutide group.Fibroblast activation was induced by TGFβ1.Cell proliferation activity was assessed using the CKK-8 kit,and cellular activity was determined using the MTT kit.Reverse transcrition-quantitative polymerase chain reaction(RT-qPCR)was utilized to quantify the level of collagen transcription,immunofluorescence staining was performed to detect the expression level of type III collagen andα-smooth muscle protein(α-SMA),and immunoblotting was conducted to monitor alterations in signal pathways.Results The addition of 10,25,50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts(P>0.05).The rate of cellular proliferation was significantly higher in the TGFβl stimulation group than in the control group.However,the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFβl-induced cell proliferation(P<0.05).The RT-qPCR results revealed that the transcription levels of type I collagen,type III collagen,andα-SMA were significantly upregulated in the TGFβl stimulation group,when compared to the control group(P<0.05).However,the expression levels of these aforementioned factors significantly decreased in the TGFβl+liraglutide group(P<0.05).The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen andα-SMA in the TGFβl stimulation group,when compared to the control group(P<0.05).However,these expression levels significantly decreased in the TGFβl+liraglutide group,when compared to the TGFβl stimulation group(P<0.05).The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFβl stimulation group,when compared to the control group(P<0.05),while these decreased in the TGFβl+liraglutide group(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway,reducing the activation and secretion of cardiac fibroblasts.展开更多
Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic he...Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.展开更多
BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographi...BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographic(ECG)markers with myocardial fibrosis identified by CMR-late gadolinium enhancement(LGE).METHODS A systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS A total of 32 studies were included.In hypertrophic cardiomyopathy(HCM),fragmented QRS(fQRS)is related to the presence and extent of myocardial fibrosis.fQRS and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients,while fQRS has also been related to fibrosis in myocarditis.Selvester score,abnormal Q waves,and notched QRS have also been associated with LGE.Repolarization abnormalities as reflected by increased Tp-Te,negative Twaves,and higher QT dispersion are related to myocardial fibrosis in HCM patients.In patients with Duchenne muscular dystrophy,a significant correlation between fQRS and the amount of myocardial fibrosis as assessed by LGE-CMR was observed.In atrial fibrillation patients,advanced inter-atrial block is defined as P-wave duration≥120 ms,and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUSION Myocardial fibrosis,a reliable marker of prognosis in a broad spectrum of cardiovascular diseases,can be easily understood with an easily applicable ECG.However,more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.展开更多
Objectives:Bioinformatics was applied to screen the key genes of Myocardial fibrosis,explore its pathogenesis and predict the potential traditional Chinese medicines for the treatment of Myocardial fibrosis.Methods:Ba...Objectives:Bioinformatics was applied to screen the key genes of Myocardial fibrosis,explore its pathogenesis and predict the potential traditional Chinese medicines for the treatment of Myocardial fibrosis.Methods:Based on raw data of gene chip GSE59437 from gene expression database(GEO),myocardial tissue samples from 3 control mice and 3 mice treated with angiotensin II-induced myocardial fibrosis were included.Using R language processing data and screening of gene express significant differences(DEG),use a database of DAVID and the R language finish Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment for differences gene,using the STRING database structure protein protein interactions(PPI)networks,using Cytoscape software visualization and use the MCODE plug-in screening key function modules in the network.Coremine Medical database was used to map the key genes,construct the gene-Chinese medicine network,and screen the traditional Chinese medicines for the treatment of myocardial fibrosis.Results:208 DEGs were screened,94 of which were up-regulated and 114 were down-regulated.DEGs is mainly involved in a variety of biological processes such as extracellular matrix remodeling,collagen fiber deposition and lipid metabolism disorders.KEGG pathway enrichment involves Platelet activation,Oxytocin signaling pathway,Insulin secretion,ECM-receptor interaction,GnRH signaling pathway,TNF signaling pathway and other signaling pathways.Key modules of PPI network including:CTGF,TIMP1,SPP1,SERPINE1,COL3A1,POSTN and FOS.The potential traditional Chinese medicines for the treatment of myocardial fibrosis are Astragalus membranaceus(Fisch.),Lepidium apetalum Willd and Salvia miltiorrhiza Bge.Conclusion:Myocardial fibrosis is a complex pathological process,and the genes related to the imbalance of extracellular matrix synthesis and degradation and excessive deposition of collagen fibers play an important role in this process.This study provides a scientific reference for further exploring the pathogenesis of myocardial fibrosis,looking for therapeutic targets and potential therapeutic traditional Chinese medicines.展开更多
Objective:To analyze the effect of candesartan and rosuvastatin on myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1...Objective:To analyze the effect of candesartan and rosuvastatin on myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1).Methods:The rats were selected as experimental samples,and these rats were randomly divided into observation group and alcohol feeding group(abbreviated as"alcohol group")and desartan combined with rosuvastatin intervention+alcoholic cardiomyopathy group(Referred to as the"intervention group"),the observation group is fed normally,the alcohol group is fed with alcohol,and the intervention group uses two drugs on the basis of the alcohol group to intervene.After 16 weeks of the three groups of experiments,analyze the results of the three groups of experiments.Myocardial structure,myocardial fibrosis and myocardial function.Results:After 16 weeks,the left ventricular short axis shortening rate(FS)and left ventricular ejection fraction in the alcohol group were lower than those in the observation group,while the collagen volume fraction(CVF)and left ventricular end-diastolic diameter(LVEDd)were higher than those in the observation group,The expression of LOX-1 in the intervention group was lower than that in the alcohol group,and the degree of fibrosis was reduced.The expression of LOX-1 in the alcohol group was higher than that in the observation group,and the degree of fiber increased.At the same time,the expression of TN-X and smad-3 protein in the alcohol group(86%±7%,83%±9%)were higher than those in the observation group(32%±10%,30%±7%),while the expression of smad-7 protein(36%±8%)was lower than that in the observation group(78%±9%),P<0.05 among the three groups of experiments,and there is statistical significance among the groups.Conclusion:Candesartan combined with Rosuvastatin can reduce myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of LOX-1.展开更多
Objective: To investigate the effect of electroacupuncture(EA) at Neiguan(PC 6) on myocardial fibrosis in spontaneously hypertensive rats(SHRs), and to explore the contribution of interleukin-1β(IL-1β),insulin-like ...Objective: To investigate the effect of electroacupuncture(EA) at Neiguan(PC 6) on myocardial fibrosis in spontaneously hypertensive rats(SHRs), and to explore the contribution of interleukin-1β(IL-1β),insulin-like growth factor 1(IGF-1), and transforming growth factor β1(TGF-β1) to the effects. Methods:Nine 12-weeks-old Wistar Kyoto(WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type Ⅰ(Col Ⅰ), collagen type Ⅲ(Col Ⅲ) and the levels of IGF-1, 1L-1β, TGF-β1,matrix metalloproteinase(MMP)-2 and MMP-9 were examined in myocardial tissure respectively. Results:After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col Ⅰ and Col Ⅲ in myocardium tissue(P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group(P<0.01). Meanwhile,the increased levels of IL-1β, IGF-1, TGF-β1 in serum or myocardial tissue of SHRs, diminished MMP 9mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment(P<0.05 or P<0.01).Furthermore, the contents of IL-1β, IGF-1, TGF-β1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively(P<0.01). Conclusion: EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1β/IGF-1-TGF-β1-MMP9 pathway.展开更多
Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the ...Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the high-salt diet(8% Na Cl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats(SS-13BN) were fed with the high-salt diet(8% Na Cl) as the negative control group. After modeling, the model rats were randomly divided into heart failure(HF) group, Shenmai Injection(SMI) group and pirfenidone(PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay(ELISA),hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. Results: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction(LVEF) and left ventricular fraction shortening(LVFS) were significantly reduced, and the serum NT-pro BNP concentration increased significantly(all P<0.05);furthermore,the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased(P<0.05);the protein and m RNA expressions of collagen type Ⅰ(Col Ⅰ) were up-regulated(P<0.05), and the mRNA expressions of transforming growth factor β1(TGF-β1), Smad2 and Smad3 were significantly up-regulated(P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly(P<0.05), and the mRNA expressions of Col Ⅰ, TGF-β1, Smad2 and Smad3, as well as Col Ⅰprotein expression, were all significantly down-regulated(all P<0.05). Conclusion: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β1/Smad signaling pathway.展开更多
MicroRNAs(miRNAs)are endogenous small non-coding RNA molecules that posttranscriptionally regulate gene expression.MiRNA expression and function in heart disease remain to be determined but modulation of miRNA express...MicroRNAs(miRNAs)are endogenous small non-coding RNA molecules that posttranscriptionally regulate gene expression.MiRNA expression and function in heart disease remain to be determined but modulation of miRNA expression in vivo has revealed that miRNAs play an important role in controlling heart function and structure.In fact,abnormal expression of miRNAs may initiate and contribute to the progress of heart disease.Here,we summarize the literature relating to the involvement of miRNAs in cardiac hypertrophy,myocardial fibrosis and heart failure.展开更多
OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound...OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound isolated from Magnolia officinalis.It possesses multiple pharmacological activities,such as anti-oxidation and anti-inflammation.This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH.METHODS①Male SD rats(220 g)were randomly divided into 5 groups(n=10):the normoxia group,the hypoxia group,the hypoxia plus Magnolol(10 and 20 mg·kg^(-1)·d-1)group,and the vehicle group.Rats in the normoxia group were kept in a normoxia environment for 4 weeks,while rats in the hypoxia group were kept in a hypoxic chamber(10%O2).The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg^(-1)(ip)once a day for 4 weeks.At the end of 4 weeks,the heart function was assessed by Doppler echocardiography,and then the rats were anesthetized with sodium pentobarbital(30 mg·kg^(-1),ip).The RVSP was measured by the right heart catheterization method.The heart tissues were collected and dissected to calculate the index of RV remodeling(RV/LV+IVS,RV/tibial length,or RV/body weight).Part of the RV samples was fixed with 4%paraformaldehyde for morphological analysis,while other samples were frozen at-80℃for molecular studies(measurements of ANP,BNP,α-SMA,and collagenⅠ/ⅢmRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels).②To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis,H9c2 or cardiac fibroblasts were divided into 7 groups:the control group,cells were cultured under normal conditions;the hypoxia group,cells were cultured under hypoxic condition(3%O2);the hypoxia plus magnolol 10 mg·kg^(-1) group,magnolol10μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg^(-1) group,magnolol 20μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group,TG-101348(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group,JSI-124(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group,an equal volume of vehicle(DMSO)was added to the culture medium before the hypoxia treatment.At the end of the experiments,the cells were collected for morphological and molecular analysis.RESULTS In vivo,male Sprang-Daley rats were exposed to 10%O2 for 4 weeks to establish an RV remodeling model,which showed hypertrophic and fibrotic features(increases of RV remodeling index,cellular size,hypertrophic and fibrotic marker expression),accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol.In vitro,the cultured H9c2 cells or cardiac fibroblasts were exposed to 3%O2 for 48 h to induce hypertrophy or fibrosis,which showed hypertrophic(increases in cellular size as well as the expression of ANP and BNP)or fibrotic features(increases in the expression of collagenⅠ,collagenⅢandα-SMA).Administration of magnolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.展开更多
Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined wit...Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.展开更多
Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chroni...Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.展开更多
Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to preve...Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to prevent or alleviate cardiac fibrosis.Curcumin,a natural molecule with antifibrotic activity,is encapsulated in the exosomes that are isolated from bone marrow-derived mesenchymal stem cells to enhance its water solubility and bioavailability.These composite exosomes are efficiently internalised by fibroblasts and effectively inhibit their transition to myofibroblasts in vitro.Decellularized porcine cardiac extracellular matrix(dECM)hydrogel is used as the carrier for delivering these composite exosomes to the infarcted myocardium,not only improving the retention of exosomes but also providing mechani-cal support and structural protection.Injection of this hydrogel into the infarcted heart of a mouse MI model leads to a decrease in collagen deposition,alleviation of fibrosis,a reduction in infarct size,and an improvement in cardiac function.The reported composite hydrogel comprising natural materials and biomolecules exhibits good biocompatibility and bioactivity.Altogether,this study demonstrates that the dECM hydrogel is a suitable platform for the local delivery of antifibrotic biomolecule-encapsulating exo-somes to prevent myocardial fibrosis after MI and have great potential for the treatment of MI in clinical settings.展开更多
BACKGROUND The prognostic value of late gadolinium enhancement(LGE)derived from cardiovascular magnetic resonance(CMR)is well studied,and several new metrics of LGE have emerged.However,some controversies remain;there...BACKGROUND The prognostic value of late gadolinium enhancement(LGE)derived from cardiovascular magnetic resonance(CMR)is well studied,and several new metrics of LGE have emerged.However,some controversies remain;therefore,further discussion is needed,and more precise risk stratification should be explored.AIM To investigate the associations between the positivity,extent,location,and pattern of LGE and multiple outcomes in dilated cardiomyopathy(DCM).METHODS PubMed,Ovid MEDLINE,and Cochrane Library were searched for studies that investigated the prognostic value of LGE in patients with DCM.Pooled hazard ratios(HRs)and 95%confidence intervals were calculated to assess the role of LGE in the risk stratification of DCM.RESULTS Nineteen studies involving 7330 patients with DCM were included in this metaanalysis and covered a wide spectrum of DCM,with a mean left ventricular ejection fraction between 21%and 50%.The meta-analysis revealed that the presence of LGE was associated with an increased risk of multiple adverse outcomes(all-cause mortality,HR:2.14;arrhythmic events,HR:5.12;and composite endpoints,HR:2.38;all P<0.001).Furthermore,every 1%increment in the extent of LGE was associated with an increased risk of all-cause mortality.Analysis of a subgroup revealed that the prognostic value varied based on different location and pattern of LGE.Additionally,we found that LGE was a stronger predictor of arrhythmic events in patients with greater left ventricular ejection fraction.CONCLUSION LGE by CMR in patients with DCM exhibited a substantial value in predicting adverse outcomes,and the extent,location,and pattern of LGE could provide additional information for risk stratification.展开更多
The fruit of Eucalyptus globulus Labill.,also known as“Yikouzhong(YKZ)”in China,belongs to the myrtaceae family.The aim of this study was to characterize the chemical composition of YKZ extract by GC-MS combined wit...The fruit of Eucalyptus globulus Labill.,also known as“Yikouzhong(YKZ)”in China,belongs to the myrtaceae family.The aim of this study was to characterize the chemical composition of YKZ extract by GC-MS combined with LC-MS/MS.A total of 34 compounds were initially identified by GC-MS and 54 compounds were identified by LC-MS/MS positive and negative total ion flow maps.The total phenols and flavonoid-like substances were quantified using an enzyme standardization method to determine the presence of phenolic substances in them.At the same time,a network pharmacology approach based on LC-MS/MS was used to construct a“drug-component-target”network for myocardial protection,and 696 potential anti-myocardial fibrosis targets were obtained.The PPI analysis identified 72 core targets,and the enrichment analysis revealed that the core targets may exert anti-myocardial fibrosis effects by regulating Lipid and atherosclerosis and Proteoglycans signaling pathways.Taken together,these results suggest that YKZ anti-cardiac fibrosis may act through multiple components and targets,and this study provides a scientific basis for the functional development and application of YKZ against myocardial fibrosis.展开更多
Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery...Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery,necrosis of myocardial cells,inflammation,and myocardial fibrosis.Aiming at the treatment of different stages of MI,in this work,an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor(VEGF)and silk fibroin(SF)microspheres containing bone morphogenetic protein 9(BMP9)for releasing VEGF and BMP9 to realize their respective functions.The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days,facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage,respectively.Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size.Taken together,these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function,showing a promising potential for cardiac clinical application.展开更多
Objective:This study aimed to explore the mechanism of Panax notoginseng(PNS)in the treatment of heart failure(HF)based on network pharmacology analysis combined with experimental verification.Materials and Methods:Th...Objective:This study aimed to explore the mechanism of Panax notoginseng(PNS)in the treatment of heart failure(HF)based on network pharmacology analysis combined with experimental verification.Materials and Methods:The potential targets and key pathways of effective components of PNS in the treatment of HF were revealed using network pharmacology.The postacute myocardial infarction(MI)HF rat model was established by ligating the left anterior descending branch of the coronary artery.The rats were divided into three groups:model,PNS,and fenofibrate groups.PNS(0.75 g/kg)and fenofibrate(10 mg/kg)were administered for 28 days.The efficacy and target mechanism of PNS in the treatment of HF were verified by cardiac ultrasound,Masson staining,and western blotting(WB)techniques.Results:The results of network pharmacology showed that seven potentially active compounds,such as quercetin,were obtained,involving 105 targets of HF;GO function was enriched to 1240 items;and KEGG enrichment covered 1240 signal pathways.The results of echocardiography showed that EF and FS of HF rats after MI were significantly increased,while Left ventricular internal dimension diastole(LVIDd)and Left ventricular internal dimension systole(LVIDs)were significantly decreased(P<0.001,P<0.05).Masson staining showed that PNS could reduce the degree of myocardial fibrosis(MF)in HF.The results of WB showed that PNS could reduce the expression of the p-p38-MAPK,transforming growth factor-beta(TGF-β),and Smad3 in HF rats.Conclusion:PNS inhibited MF and treated HF by regulating p-p38 MAPK-TGF-βpathway,which lays a theoretical foundation for further study of its pharmacological mechanism and key target.展开更多
基金the China’s National Key Research and Development Program Projects(No.2022YFC3500500 and No.2022YFC3500502).
文摘Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.
基金the Health Commission of Hebei Province,No.20220998.
文摘BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling.Macrophages polarize to two distinct phenotypes:M1 and M2,and such plasticity in phenotypes provide macrophages various biological functions.AIM To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.METHODS DCM mouse models were established and randomly divided into DM,atorvastatin,and metformin groups.C57BL/6 mice were used as the control.Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues.The expression of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),M1 macrophages(iNOS^(+)),and M2 macrophages(CD206^(+))were demonstrated by immunohistochemistry and immunofluorescence staining.The levels of TGF-β1,IL-1β,and TNF-αwere detected by ELISA and real-time quantitative polymerase chain reaction.Malondialdehyde(MDA)concentrations and superoxide dismutase(SOD)activities were also measured.RESULTS Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardialfibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment.Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin;lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium;decreased the concentration of MDAand increased SOD activity in myocardium of db/db mice;inhibited M1 macrophages;and promoted M2macrophages.CONCLUSION Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with theantioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulatingmacrophage polarization.
基金supported by grants from the Natural Science Foundation of Hubei Province(No.2022CFB671)Health Research Project of Hubei Province(No.WJ2023F020)Hubei Province Key Laboratory Open Project(No.2021KFY023).
文摘Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myocardial fibrosis remains unexplored.The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts.Methods Primary rat adult fibroblasts were isolated,cultured,and randomly allocated into 4 groups:control group,transforming growth factor beta1(TGFβ1)stimulation group,liraglutide group,and TGFβ1+liraglutide group.Fibroblast activation was induced by TGFβ1.Cell proliferation activity was assessed using the CKK-8 kit,and cellular activity was determined using the MTT kit.Reverse transcrition-quantitative polymerase chain reaction(RT-qPCR)was utilized to quantify the level of collagen transcription,immunofluorescence staining was performed to detect the expression level of type III collagen andα-smooth muscle protein(α-SMA),and immunoblotting was conducted to monitor alterations in signal pathways.Results The addition of 10,25,50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts(P>0.05).The rate of cellular proliferation was significantly higher in the TGFβl stimulation group than in the control group.However,the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFβl-induced cell proliferation(P<0.05).The RT-qPCR results revealed that the transcription levels of type I collagen,type III collagen,andα-SMA were significantly upregulated in the TGFβl stimulation group,when compared to the control group(P<0.05).However,the expression levels of these aforementioned factors significantly decreased in the TGFβl+liraglutide group(P<0.05).The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen andα-SMA in the TGFβl stimulation group,when compared to the control group(P<0.05).However,these expression levels significantly decreased in the TGFβl+liraglutide group,when compared to the TGFβl stimulation group(P<0.05).The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFβl stimulation group,when compared to the control group(P<0.05),while these decreased in the TGFβl+liraglutide group(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway,reducing the activation and secretion of cardiac fibroblasts.
基金This study was supported by grants from Scientific Research Development Program of North Sichuan Medical College(No.CBY16-A-ZD10)Nanchong Government-University Strategic Cooperation Project in Science and Technology(No.18SXHZ0505).
文摘Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.
文摘BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographic(ECG)markers with myocardial fibrosis identified by CMR-late gadolinium enhancement(LGE).METHODS A systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS A total of 32 studies were included.In hypertrophic cardiomyopathy(HCM),fragmented QRS(fQRS)is related to the presence and extent of myocardial fibrosis.fQRS and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients,while fQRS has also been related to fibrosis in myocarditis.Selvester score,abnormal Q waves,and notched QRS have also been associated with LGE.Repolarization abnormalities as reflected by increased Tp-Te,negative Twaves,and higher QT dispersion are related to myocardial fibrosis in HCM patients.In patients with Duchenne muscular dystrophy,a significant correlation between fQRS and the amount of myocardial fibrosis as assessed by LGE-CMR was observed.In atrial fibrillation patients,advanced inter-atrial block is defined as P-wave duration≥120 ms,and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUSION Myocardial fibrosis,a reliable marker of prognosis in a broad spectrum of cardiovascular diseases,can be easily understood with an easily applicable ECG.However,more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.
基金National Natural Science Foundation of China(No.81573916)Special Project for Business Construction and Scientific Research of National Clinical Research Base of Traditional Chinese Medicine(No.JDZX2015141)+2 种基金Shandong Taishan Scholar Construction Project Special Fund(No.2018-35)Natural Science Foundation of Shandong Province(No.ZR201911140060)Shandong Science and Technology Development Plan of Traditional Chinese Medicine(No.2019-0191)。
文摘Objectives:Bioinformatics was applied to screen the key genes of Myocardial fibrosis,explore its pathogenesis and predict the potential traditional Chinese medicines for the treatment of Myocardial fibrosis.Methods:Based on raw data of gene chip GSE59437 from gene expression database(GEO),myocardial tissue samples from 3 control mice and 3 mice treated with angiotensin II-induced myocardial fibrosis were included.Using R language processing data and screening of gene express significant differences(DEG),use a database of DAVID and the R language finish Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment for differences gene,using the STRING database structure protein protein interactions(PPI)networks,using Cytoscape software visualization and use the MCODE plug-in screening key function modules in the network.Coremine Medical database was used to map the key genes,construct the gene-Chinese medicine network,and screen the traditional Chinese medicines for the treatment of myocardial fibrosis.Results:208 DEGs were screened,94 of which were up-regulated and 114 were down-regulated.DEGs is mainly involved in a variety of biological processes such as extracellular matrix remodeling,collagen fiber deposition and lipid metabolism disorders.KEGG pathway enrichment involves Platelet activation,Oxytocin signaling pathway,Insulin secretion,ECM-receptor interaction,GnRH signaling pathway,TNF signaling pathway and other signaling pathways.Key modules of PPI network including:CTGF,TIMP1,SPP1,SERPINE1,COL3A1,POSTN and FOS.The potential traditional Chinese medicines for the treatment of myocardial fibrosis are Astragalus membranaceus(Fisch.),Lepidium apetalum Willd and Salvia miltiorrhiza Bge.Conclusion:Myocardial fibrosis is a complex pathological process,and the genes related to the imbalance of extracellular matrix synthesis and degradation and excessive deposition of collagen fibers play an important role in this process.This study provides a scientific reference for further exploring the pathogenesis of myocardial fibrosis,looking for therapeutic targets and potential therapeutic traditional Chinese medicines.
基金Xi'an Science and Technology Plan Project.Study on digestive,cardio-cerebrovascular system diseases-Study on the correlation between LOX-1 and myocardial fibrosis in alcoholic cardiomyopathy(Project No.:201805094YX2SF28(9)).
文摘Objective:To analyze the effect of candesartan and rosuvastatin on myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1).Methods:The rats were selected as experimental samples,and these rats were randomly divided into observation group and alcohol feeding group(abbreviated as"alcohol group")and desartan combined with rosuvastatin intervention+alcoholic cardiomyopathy group(Referred to as the"intervention group"),the observation group is fed normally,the alcohol group is fed with alcohol,and the intervention group uses two drugs on the basis of the alcohol group to intervene.After 16 weeks of the three groups of experiments,analyze the results of the three groups of experiments.Myocardial structure,myocardial fibrosis and myocardial function.Results:After 16 weeks,the left ventricular short axis shortening rate(FS)and left ventricular ejection fraction in the alcohol group were lower than those in the observation group,while the collagen volume fraction(CVF)and left ventricular end-diastolic diameter(LVEDd)were higher than those in the observation group,The expression of LOX-1 in the intervention group was lower than that in the alcohol group,and the degree of fibrosis was reduced.The expression of LOX-1 in the alcohol group was higher than that in the observation group,and the degree of fiber increased.At the same time,the expression of TN-X and smad-3 protein in the alcohol group(86%±7%,83%±9%)were higher than those in the observation group(32%±10%,30%±7%),while the expression of smad-7 protein(36%±8%)was lower than that in the observation group(78%±9%),P<0.05 among the three groups of experiments,and there is statistical significance among the groups.Conclusion:Candesartan combined with Rosuvastatin can reduce myocardial fibrosis in rats with alcoholic cardiomyopathy by mediating the expression of LOX-1.
基金Supported by the National Natural Science Foundation of China(No.81804211,No.81774439)China Academy of Chinese Medical Sciences Foundation(No.ZZ13-YQ-065)。
文摘Objective: To investigate the effect of electroacupuncture(EA) at Neiguan(PC 6) on myocardial fibrosis in spontaneously hypertensive rats(SHRs), and to explore the contribution of interleukin-1β(IL-1β),insulin-like growth factor 1(IGF-1), and transforming growth factor β1(TGF-β1) to the effects. Methods:Nine 12-weeks-old Wistar Kyoto(WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type Ⅰ(Col Ⅰ), collagen type Ⅲ(Col Ⅲ) and the levels of IGF-1, 1L-1β, TGF-β1,matrix metalloproteinase(MMP)-2 and MMP-9 were examined in myocardial tissure respectively. Results:After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col Ⅰ and Col Ⅲ in myocardium tissue(P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group(P<0.01). Meanwhile,the increased levels of IL-1β, IGF-1, TGF-β1 in serum or myocardial tissue of SHRs, diminished MMP 9mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment(P<0.05 or P<0.01).Furthermore, the contents of IL-1β, IGF-1, TGF-β1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively(P<0.01). Conclusion: EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1β/IGF-1-TGF-β1-MMP9 pathway.
基金Supported by Hunan Provincial Natural Science Foundation of China(No.2020JJ5408)Scientific Research Fund of Hunan Provincial Education Department(No.21B0361)+1 种基金Research Fund of Hunan University of Chinese Medicine(No.2019XJJJ012)Zhuzhou Second Batch of Science and Technology Guidance Projects(No.2017-17)。
文摘Objective: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. Methods: Salt-sensitive(Dahl/SS) rats were fed with normal diet(0.3% Na Cl) and the high-salt diet(8% Na Cl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats(SS-13BN) were fed with the high-salt diet(8% Na Cl) as the negative control group. After modeling, the model rats were randomly divided into heart failure(HF) group, Shenmai Injection(SMI) group and pirfenidone(PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay(ELISA),hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. Results: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction(LVEF) and left ventricular fraction shortening(LVFS) were significantly reduced, and the serum NT-pro BNP concentration increased significantly(all P<0.05);furthermore,the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased(P<0.05);the protein and m RNA expressions of collagen type Ⅰ(Col Ⅰ) were up-regulated(P<0.05), and the mRNA expressions of transforming growth factor β1(TGF-β1), Smad2 and Smad3 were significantly up-regulated(P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly(P<0.05), and the mRNA expressions of Col Ⅰ, TGF-β1, Smad2 and Smad3, as well as Col Ⅰprotein expression, were all significantly down-regulated(all P<0.05). Conclusion: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β1/Smad signaling pathway.
基金supported by the China Postdoctoral Special Science Foundation,the Foundation for the Author of a National Excellent Doctoral Dissertation of P.R.China(2007B72)the National Basic Research Program of China(2007CB512006)。
文摘MicroRNAs(miRNAs)are endogenous small non-coding RNA molecules that posttranscriptionally regulate gene expression.MiRNA expression and function in heart disease remain to be determined but modulation of miRNA expression in vivo has revealed that miRNAs play an important role in controlling heart function and structure.In fact,abnormal expression of miRNAs may initiate and contribute to the progress of heart disease.Here,we summarize the literature relating to the involvement of miRNAs in cardiac hypertrophy,myocardial fibrosis and heart failure.
文摘OBJECTIVE Right ventricular(RV)remodeling is one of the essential pathological features in pulmonary arterial hypertension(PAH).RV hypertrophy or fibrosis are the leading causes of RV remodeling.Magnolol is a compound isolated from Magnolia officinalis.It possesses multiple pharmacological activities,such as anti-oxidation and anti-inflammation.This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH.METHODS①Male SD rats(220 g)were randomly divided into 5 groups(n=10):the normoxia group,the hypoxia group,the hypoxia plus Magnolol(10 and 20 mg·kg^(-1)·d-1)group,and the vehicle group.Rats in the normoxia group were kept in a normoxia environment for 4 weeks,while rats in the hypoxia group were kept in a hypoxic chamber(10%O2).The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg^(-1)(ip)once a day for 4 weeks.At the end of 4 weeks,the heart function was assessed by Doppler echocardiography,and then the rats were anesthetized with sodium pentobarbital(30 mg·kg^(-1),ip).The RVSP was measured by the right heart catheterization method.The heart tissues were collected and dissected to calculate the index of RV remodeling(RV/LV+IVS,RV/tibial length,or RV/body weight).Part of the RV samples was fixed with 4%paraformaldehyde for morphological analysis,while other samples were frozen at-80℃for molecular studies(measurements of ANP,BNP,α-SMA,and collagenⅠ/ⅢmRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels).②To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis,H9c2 or cardiac fibroblasts were divided into 7 groups:the control group,cells were cultured under normal conditions;the hypoxia group,cells were cultured under hypoxic condition(3%O2);the hypoxia plus magnolol 10 mg·kg^(-1) group,magnolol10μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg^(-1) group,magnolol 20μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group,TG-101348(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group,JSI-124(a specific inhibitor of JAK2)1μmol·L^(-1) was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group,an equal volume of vehicle(DMSO)was added to the culture medium before the hypoxia treatment.At the end of the experiments,the cells were collected for morphological and molecular analysis.RESULTS In vivo,male Sprang-Daley rats were exposed to 10%O2 for 4 weeks to establish an RV remodeling model,which showed hypertrophic and fibrotic features(increases of RV remodeling index,cellular size,hypertrophic and fibrotic marker expression),accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol.In vitro,the cultured H9c2 cells or cardiac fibroblasts were exposed to 3%O2 for 48 h to induce hypertrophy or fibrosis,which showed hypertrophic(increases in cellular size as well as the expression of ANP and BNP)or fibrotic features(increases in the expression of collagenⅠ,collagenⅢandα-SMA).Administration of magnolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.
基金National natural science foundation of China(No.81973844)。
文摘Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.
基金supported by grants from the National Natural Science Foundation of China(No.81441016)and Key R&D Plan in Shaanxi Province of China(No.2020SF-262 and No.2019SF-200).
文摘Objective Cardiac fibroblasts(CFs)proliferation and extracellular matrix deposition are important features of cardiac fibrosis.Various studies have indicated that vitamin D displays an anti-fibrotic property in chronic heart diseases.This study explored the role of vitamin D in the growth of CFs via an integrin signaling pathway.Methods MTT and 5-ethynyl-2′-deoxyuridine assays were performed to determine cell viability.Western blotting was performed to detect the expression of proliferating cell nuclear antigen(PCNA)and integrin signaling pathway.The fibronectin was observed by ELISA.Immunohistochemical staining was employed to evaluate the expression of integrinβ3.Results The PCNA expression in the CFs was enhanced after isoproterenol(ISO)stimulation accompanied by an elevated expression of integrin beta-3(β3).The blockade of the integrinβ3 with a specific integrinβ3 antibody reduced the PCNA expression induced by the ISO.Decreasing the integrinβ3 by siRNA reduced the ISO-triggered phosphorylation of FAK and Akt.Both the FAK inhibitor and Akt inhibitor suppressed the PCNA expression induced by the ISO in the CFs.Calcitriol(CAL),an active form of vitamin D,attenuated the ISO-induced CFs proliferation by downregulating the integrinβ3 expression,and phosphorylation of FAK and Akt.Moreover,CAL reduced the increased levels of fibronectin and hydroxyproline in the CFs culture medium triggered by the ISO.The administration of calcitriol decreased the integrinβ3 expression in the ISO-induced myocardial injury model.Conclusion These findings revealed a novel role for CAL in suppressing the CFs growth by the downregulation of the integrinβ3/FAK/Akt pathway.
基金supported by the National Natural Science Foun-dation of China(no.92168203)Jiangsu Cardiovascular Medicine Innovation Center(no.CXZX202210)+1 种基金the Scientific Research In-novation Project for Graduate Students of Jiangsu Province(no.KYCX22_3189)the Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function,Soochow University,and the Priority Academic Program Development of Jiangsu Higher Ed-ucation Institutions(PAPD).
文摘Excessive cardiac fibrosis impairs cardiac repair after myocardial infarction(MI).In this work,an in-jectable composite hydrogel integrating natural biomaterials,exosomes,and bioactive molecules is de-veloped to prevent or alleviate cardiac fibrosis.Curcumin,a natural molecule with antifibrotic activity,is encapsulated in the exosomes that are isolated from bone marrow-derived mesenchymal stem cells to enhance its water solubility and bioavailability.These composite exosomes are efficiently internalised by fibroblasts and effectively inhibit their transition to myofibroblasts in vitro.Decellularized porcine cardiac extracellular matrix(dECM)hydrogel is used as the carrier for delivering these composite exosomes to the infarcted myocardium,not only improving the retention of exosomes but also providing mechani-cal support and structural protection.Injection of this hydrogel into the infarcted heart of a mouse MI model leads to a decrease in collagen deposition,alleviation of fibrosis,a reduction in infarct size,and an improvement in cardiac function.The reported composite hydrogel comprising natural materials and biomolecules exhibits good biocompatibility and bioactivity.Altogether,this study demonstrates that the dECM hydrogel is a suitable platform for the local delivery of antifibrotic biomolecule-encapsulating exo-somes to prevent myocardial fibrosis after MI and have great potential for the treatment of MI in clinical settings.
基金the Research Grant of the National Natural Science Foundation of China,No.81801674Sichuan Province Science and Technology Support Program,No.2021YJ0242.
文摘BACKGROUND The prognostic value of late gadolinium enhancement(LGE)derived from cardiovascular magnetic resonance(CMR)is well studied,and several new metrics of LGE have emerged.However,some controversies remain;therefore,further discussion is needed,and more precise risk stratification should be explored.AIM To investigate the associations between the positivity,extent,location,and pattern of LGE and multiple outcomes in dilated cardiomyopathy(DCM).METHODS PubMed,Ovid MEDLINE,and Cochrane Library were searched for studies that investigated the prognostic value of LGE in patients with DCM.Pooled hazard ratios(HRs)and 95%confidence intervals were calculated to assess the role of LGE in the risk stratification of DCM.RESULTS Nineteen studies involving 7330 patients with DCM were included in this metaanalysis and covered a wide spectrum of DCM,with a mean left ventricular ejection fraction between 21%and 50%.The meta-analysis revealed that the presence of LGE was associated with an increased risk of multiple adverse outcomes(all-cause mortality,HR:2.14;arrhythmic events,HR:5.12;and composite endpoints,HR:2.38;all P<0.001).Furthermore,every 1%increment in the extent of LGE was associated with an increased risk of all-cause mortality.Analysis of a subgroup revealed that the prognostic value varied based on different location and pattern of LGE.Additionally,we found that LGE was a stronger predictor of arrhythmic events in patients with greater left ventricular ejection fraction.CONCLUSION LGE by CMR in patients with DCM exhibited a substantial value in predicting adverse outcomes,and the extent,location,and pattern of LGE could provide additional information for risk stratification.
基金supported by the National Natural Science Foundation of China(grant No.81703389)The Training Program for Excellent Young Innovators of Changsha(kq2206054)+3 种基金Education Fund Item of Liaoning Province(LJKZ0906)Natural Science Foundation of Science and Technology Department of Liaoning Province(2021-MS-215)Youth Development Support Plan of Shenyang Pharmaceutical University(ZQN2021010)And Natural Science Fund of Hunan Province(No.2022JJ30638).
文摘The fruit of Eucalyptus globulus Labill.,also known as“Yikouzhong(YKZ)”in China,belongs to the myrtaceae family.The aim of this study was to characterize the chemical composition of YKZ extract by GC-MS combined with LC-MS/MS.A total of 34 compounds were initially identified by GC-MS and 54 compounds were identified by LC-MS/MS positive and negative total ion flow maps.The total phenols and flavonoid-like substances were quantified using an enzyme standardization method to determine the presence of phenolic substances in them.At the same time,a network pharmacology approach based on LC-MS/MS was used to construct a“drug-component-target”network for myocardial protection,and 696 potential anti-myocardial fibrosis targets were obtained.The PPI analysis identified 72 core targets,and the enrichment analysis revealed that the core targets may exert anti-myocardial fibrosis effects by regulating Lipid and atherosclerosis and Proteoglycans signaling pathways.Taken together,these results suggest that YKZ anti-cardiac fibrosis may act through multiple components and targets,and this study provides a scientific basis for the functional development and application of YKZ against myocardial fibrosis.
基金This work was supported by the National Natural Science Foundation of China(91839101,21774086,81770258,81900317)the Suzhou Municipal Science and Technology Foundation(SYS2018026)the Introduction Project of Clinical Medicine Expert Team for Suzhou(SZYJTD201704).
文摘Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human health.The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery,necrosis of myocardial cells,inflammation,and myocardial fibrosis.Aiming at the treatment of different stages of MI,in this work,an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor(VEGF)and silk fibroin(SF)microspheres containing bone morphogenetic protein 9(BMP9)for releasing VEGF and BMP9 to realize their respective functions.The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days,facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage,respectively.Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size.Taken together,these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function,showing a promising potential for cardiac clinical application.
基金supported by the National Natural Science Foundation of China(grant number 81822049)the Major New Drug Creation of the Ministry of Science and Technology(grant number 2019ZX09201004-001-011)。
文摘Objective:This study aimed to explore the mechanism of Panax notoginseng(PNS)in the treatment of heart failure(HF)based on network pharmacology analysis combined with experimental verification.Materials and Methods:The potential targets and key pathways of effective components of PNS in the treatment of HF were revealed using network pharmacology.The postacute myocardial infarction(MI)HF rat model was established by ligating the left anterior descending branch of the coronary artery.The rats were divided into three groups:model,PNS,and fenofibrate groups.PNS(0.75 g/kg)and fenofibrate(10 mg/kg)were administered for 28 days.The efficacy and target mechanism of PNS in the treatment of HF were verified by cardiac ultrasound,Masson staining,and western blotting(WB)techniques.Results:The results of network pharmacology showed that seven potentially active compounds,such as quercetin,were obtained,involving 105 targets of HF;GO function was enriched to 1240 items;and KEGG enrichment covered 1240 signal pathways.The results of echocardiography showed that EF and FS of HF rats after MI were significantly increased,while Left ventricular internal dimension diastole(LVIDd)and Left ventricular internal dimension systole(LVIDs)were significantly decreased(P<0.001,P<0.05).Masson staining showed that PNS could reduce the degree of myocardial fibrosis(MF)in HF.The results of WB showed that PNS could reduce the expression of the p-p38-MAPK,transforming growth factor-beta(TGF-β),and Smad3 in HF rats.Conclusion:PNS inhibited MF and treated HF by regulating p-p38 MAPK-TGF-βpathway,which lays a theoretical foundation for further study of its pharmacological mechanism and key target.
