Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether n...Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.展开更多
In ischemic hypertrophic myocardium, contractile dysfunction can be attributed to the decreased calcium induced calcium release (CICR) in cytoplasm. This study aimed to investigate the electrophysiological properties ...In ischemic hypertrophic myocardium, contractile dysfunction can be attributed to the decreased calcium induced calcium release (CICR) in cytoplasm. This study aimed to investigate the electrophysiological properties and the expression of L calcium channel subunits in post-MI myocardium. The ischemic heart remodeling model was established in SD rats. The expressions of calcium channel subunits were determined by realtime RT-PCR. Whole cell patch clamp was used to record the electrophysiological properties of L calcium channel. The results showed that the L calcium channel agonist Bayk 8644 induced the significantly decreased CICR in the rat cardiomyocyte 6 weeks after myocardial infarction (MI). In the post-MI cardiomyocytes, the amplitude of ICaL decreased dramatically and the inactivation curve of the current shifted to more negative potential. At mRNA level, the expression of the calcium channel alpha1c, beta2c subunits decreased dramatically in the ventricle of post-MI rats. The expression of alpha2/delta subunit, however, remained constant. It is concluded that the abnormal expression of the L calcium channel subunits in post-MI cardiomyocytes contributes to the ICaL decrease at early stage of the ischemic remodeling in cardiomyocytes, which leads to the decreased CICR in the cell and contractile dysfunction of myocardium.展开更多
Myocardial fiber deformation measurements have been reported to be associated with adverse outcomes in patients with acute heart failure and those with myocardial infarction.However,few studies have addressed the prog...Myocardial fiber deformation measurements have been reported to be associated with adverse outcomes in patients with acute heart failure and those with myocardial infarction.However,few studies have addressed the prognostic value of global circumferential strain(GCS)in dilated cardiomyopathy(DCM)patients with severely impaired systolic function.This study aimed to evaluate the prognostic value of cardiac magnetic resonance(CMR)-derived GCS in DCM patients with severely reduced ejection.Consecutive DCM patients with severely reduced ejection fraction(EF<35%)who underwent CMR were included.GCS was calculated from CMR cine images.The clinical endpoint was a composite of all-cause mortality,heart transplantation,implantable cardioverter defibrillator(ICD)implantation and aborted sudden cardiac death(SCD).A total of 129 patients with a mean EF of 15.33%(11.36%–22.27%)were included.During a median follow-up of 518 days,endpoint events occurred in 50 patients.Patients with GCS≥the median(−5.17%)had significantly reduced event-free survival as compared with those with GCS<the median(P<0.01).GCS was independently associated with adverse events after adjusting for clinical and imaging risk factors including extent of late gadolinium enhancement(LGE)(P<0.05).Adding GCS into the model including the extent of LGE resulted in significant improvements in the C-statistic(from 0.706 to 0.742;P<0.05)with a continuous net reclassification improvement(NRI)of 29.71%.It was concluded that GCS derived from CMR could be useful for risk stratification in DCM patients with severely reduced EF,which may increase common imaging risk factors including LGE.展开更多
The antibody against AT1-EC2 plays a role in some kinds of inflammatory vascular diseases including malignant hypertension,preeclampsia,and renal-allograft rejection,but the detailed mechanisms remain unclear.In order...The antibody against AT1-EC2 plays a role in some kinds of inflammatory vascular diseases including malignant hypertension,preeclampsia,and renal-allograft rejection,but the detailed mechanisms remain unclear.In order to investigate the changes of NADPH oxidase and reactive oxygen species in the aorta in a mouse model which can produce AT1-EC2 antibody by active immunization with AT1-EC2 peptide,15 mice were divided into three groups:control group,AT1-EC2-immunized group,and AT1-EC2-immunized and valsartan-treated group.In AT1-EC2-immunized group and AT1-EC2-immunized and valsartan-treated group,the mice were immunized by 50 μg peptide subcutaneously at multiple points for 4 times:0,5,10,and 15 days after the experiment.In AT1-EC2-immunized and valsartan-treated group,valsartan was given at a dose of 100 mg/kg every day for 20 days.After the experiment,the mice were sacrificed under anesthesia and the aortas were obtained and frozen in liquid nitrogen for the preparation of frozen section slides and other experiments.The titer of AT1-EC2 was assayed by using ELISA.The level of NOX1 mRNA in the aorta was determined by using RT-PCR.The expression of NOX1 was detected by using Western blotting.Confocal scanning microscopy was used to assay the α-actin and NOX1 expression in the aortic tissue.The O 2.production was detected in situ after DHE staining.The mice produced high level antibody against AT1-EC2 in AT1-EC2-immunized group and AT1-EC2-immunized and valsartan-treated group,and the level of NOX1 mRNA in the aortic tissues was 1.6±0.4 times higher and the NOX1 protein expression was higher in AT1-EC2-immunized group than in control group.There were no significant differences in the level of NOX1 mRNA and protein expression between control group and AT1-EC2-immunized and valsartan-treated group.The expression and co-localization of α-actin and NOX1 in AT1-EC2-immunized group increased significantly as compared with those in control group,and the O 2.production increased about 2.7 times as compared with control group.There were no significant differences between control group and AT1-EC2-immunized and valsartan-treated group.It is concluded that active immunization with AT1-EC2 can activate NOX1-ROS,and increase vascular inflammation,which can be inhibited by AT1 receptor blocker valsartan.This may partially explain the mechanism of the pathogenesis of inflammatory vascular diseases related to antibody against AT1-EC2.展开更多
Poly(ADP-ribose) polymerase 1 (PARP1) plays important roles in the regulation of transcription factors. Mounting evidence has shown that inhibition of PARP1 influences the expression of genes associated with inflammat...Poly(ADP-ribose) polymerase 1 (PARP1) plays important roles in the regulation of transcription factors. Mounting evidence has shown that inhibition of PARP1 influences the expression of genes associated with inflammatory response. Interferon regulatory factor 1 (IRF1) is a critical transcription factor for the development of both the innate and adaptive immune responses against infections. However, the molecular mechanism through which PARP1 mediates the effects has not been clearly demonstrated. Jurkat cells were exposed to dexamethasone (Dex) or PARP1 inhibitor PJ34. The expression levels of IL-12, LMP2, OAS1 and PKR were detected using real-time RT-PCR. The interactions between PARP1 and IRF1 were examined by coimmunoprecipitation (co-IP) assays. We further explored the mechanism of PARP1 suppressing IRF1 by assessing the activities of interferon stimulated response element (ISRE). The mRNA expression of IL-12, LMP2, OAS1 and PKR was obviously suppressed by Dex in Jurkat cells, which could be rescued by PJ34 treatment. Luciferase study revealed that poly(ADP-ribosyl)- ation suppressed IRF1-mediated transcription through preventing the binding of IRF1 to ISREs. PARP1 inhibited IRF1-mediated transcription in Jurkat cells by preventing IRF1 binding to ISREs in the promoters of target genes. It is suggested that PARP1 is a crucial regulator of IRF1-mediated immune response. This study provides experimental evidence for the possible application of PARP1 inhibitors in the treatment of IRF1-related immune anergy.展开更多
To observe the dynamic changes of the TGF-β1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relation...To observe the dynamic changes of the TGF-β1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively. The relative levels of mRNA of TGF-β1, collagen type Ⅰ, Ⅲ, and fetal gene beta-MHC were de- tected by RT-PCR. The distribution of TGF-β1 protein in the myocardium was detected by immuno- histochemistry. The results showed that the size of infarction was higher than that of the sham oper- ated groups in the infarcted group (44.5±0.5 vs 0). The difference in hemodynamic parameters be- tween the infarcted group and sham operated group was significant (P<0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day, which lasted 4 weeks. Then, it decreased gradually. β-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type Ⅰ /Ⅲ showed similar changes as compared with the sham operated groups (P<0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P<0.01) at day 180. Linear regression analysis indicated that the TGF-β1 was posi- tively correlated with the ventricular remodeling.It was concluded that the cytokine TGF-β1 par- ticipates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.展开更多
Objective: To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation (A/R) injury of neonatal rat. Methods:The model of A/R injury was finished through receiving anoxia for 2 h and ...Objective: To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation (A/R) injury of neonatal rat. Methods:The model of A/R injury was finished through receiving anoxia for 2 h and reoxygenation for 4 h in cultured cardiomyocytes of neonatal rat. The cardiomyocytes were divided randomly into 3 groups: control group (CON), anoxia/reoxygenation group (A/R) and insulin-treated group (INS). At the end of reoxygenation of 4 hours, activities of lactate dehydrogenase (LDH), contents of malondialdehyde (MDA) were assessed through spectrophotometric procedures, myocyte apoptosis were detected through TUNEL and DNA Ladder. Results: MDA, LDH, and Apoptosis Index were significantly decreased in INS group compared with A/R group (P<0.01). Conclusion: Insulin has a protective effect against A/R injury in cultured cardiomyocyte of neonatal rat; the protective mechanism may contribute to antiapoptosis of insulin.展开更多
The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granu...The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class Ⅱ and CD86. Supernatants were analyzed for the production of IL-12 and IFN-γ cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-γ production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.展开更多
In order to study the expression of IL-1β and TNF-α in the myocardium of MCMV myocarditis and their role in the myocardial damages, 60 BALB/C mice of 4 weeks were randomly divided into two groups: 36 were injected i...In order to study the expression of IL-1β and TNF-α in the myocardium of MCMV myocarditis and their role in the myocardial damages, 60 BALB/C mice of 4 weeks were randomly divided into two groups: 36 were injected intraperitoneally with MCMV and 24 served as control group. Immunohistochemistry was used to detect IL-1β and TNF-α expression in the myocardium, and myocardial lesions were observed histopathologically. Histopathological study on the myocardium from infected mice revealed focal or diffuse lesions characterized by inflammatory cells and degeneration or necrosis of myocytes. The myocardial lesion score showed the degree of inflammatory cell infiltration was slight in MCMV myocarditis.The positive staining signals for IL-1β and TNF-α proteins which mainly located in the infiltrating inflammatory cells and degenerative or necrotic myocytes were markedly detectable whereas there were no positive findings in the myocardium of control mice. IL-1β and TNF-α was expressed in the myocardium of viral myocarditis murine model induced by MCMV. IL-1β and TNF-α may play an important role in the pathogenesis of viral myocarditis.展开更多
Autonomic nervous system activation can result in significant changes of atrial electrophysiology and facilitate induction of atrial fibrillation. By recording influence of different concentrations of acetylcholine (A...Autonomic nervous system activation can result in significant changes of atrial electrophysiology and facilitate induction of atrial fibrillation. By recording influence of different concentrations of acetylcholine (ACh) on atrial fibers (AF), we investigated the role of the increased vagal tone in electrical remodeling in atrial fibrillation. Parameters of action potentials and force contraction (Fc) in atrial fibers were recorded by using standard intracellular microelectrode technique and force transducer. It was found that: (1) ACh at 0.1 μmol/L had no significant influence on spontaneous action potentials (SAPs) and Fc (n=6, P>0.05); ACh at both 1.0 and 10.0 μmol/L shortened action potential duration (APD) and Fc of human AF from right atrium (n=6, P<0.05); there was no significant difference in shortening APD between 10.0 and 1.0 μmol/L of ACh; (2) ACh at 0.1 μmol/L had no significant desensitization (n=6, P>0.05), but ACh at 1.0 and 10.0 μmol/L had desensitization (n=6, P<0.05) to SAPs and Fc. The desensitization of ACh on APD in AF was concentration- and time-dependent. It was shown that APD was longer than the control along with extending time of continuous Tyrode's solution perfusion after desensitization. It is concluded that ACh changes the electrophysiological characteristics of human AF, indicating that increased vagal tone plays a role in the development of a vulnerable substrate for atrial electrical remodeling in atrial fibrillation.展开更多
Regulatory T cells(Tregs) play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or ac...Regulatory T cells(Tregs) play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function,however,little has been known about its role in hypertension.This study was aimed to find whether Helios+ Tregs really play a vital role in hypertension.A total of 60 hypertension patients,and 46 normotension subjects were enrolled in this study.Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry.Plasma cytokine level was determined by ELISA.The m RNA expression of Foxp3 and Helios in purified CD4+ T cells was detected by RT-PCR.Proportion of CD4+Foxp3+Helios+ Tregs was decreased significantly in patients with hypertension(62.52%±1.18% vs.71.89%±1.03%,P<0.01),and it was correlated with plasma level of IL-10 positively(r=0.505,P<0.05) and plasma level of IFN-gamma negatively(r=–0.551,P<0.05).The m RNA expression of Foxp3(7.23±1.00 vs.10.58±0.54,P<0.05) and Helios(8.47±0.95 vs.15.52±2.0,P<0.05) was decreased in CD4+ T cells from patients with hypertension.Helios+ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.展开更多
The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice t...The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6–8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P<0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P<0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.展开更多
Objectives To study the depressive effect of the antisense oligonuceotides (ASODN) of c-myc and proliferating cell nuclear antigen (PCNA) on the proliferation of VSMC. Methods Taking the VSMC obtained from rat aorta t...Objectives To study the depressive effect of the antisense oligonuceotides (ASODN) of c-myc and proliferating cell nuclear antigen (PCNA) on the proliferation of VSMC. Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4～8 generation as research object. The objects were divided into three groups to carry out control study: control group, PCNA ASODN group and c-myc ASODN group. The ASODNs' working concentration all were 1:50. The depressive effect of ASODN on VSMC proliferation was investigated by cell counting, MTT and 3H-TdR incorporation assay; PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA and c-myc ASODN into VSMC. Results PCNA and c-myc ASODN could inhibit the proliferation of VSMC significantly, compared with control group (P<0.05). ② Transferring PCNA and c-myc ASODN into VSMC obtained successfully; the corresponding gene was inhibited obviously; compared with control group (P<0.05). Conclusions PCNA and c-myc might play a considerable role in the VSMC proliferation process. The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC, and then the proliferation of VSMC was slowed down. This study presented a beneficial proposal and theoretical fundament for atherosclerotic treatment.展开更多
The opening of mitochondrial permeability transition pore(MPTP) plays a critical role in platelet activation. However,the potential trigger of the MPTP opening in platelet activation remains unknown. Inflammation is t...The opening of mitochondrial permeability transition pore(MPTP) plays a critical role in platelet activation. However,the potential trigger of the MPTP opening in platelet activation remains unknown. Inflammation is the crucial trigger of platelet activation. In this study,we aimed to explore whether and how the important inflammatory cytokine IL-17 is associated with MPTP opening in platelets activation by using MPTP inhibitor cyclosporine-A(Cs A). The mitochondrial membrane potential(Δψm) was detected to reflect MPTP opening levels. And the platelet aggregation,activation,and the primary signaling pathway were also tested. The results showed that the MPTP opening levels were increased and Δψm reduced in platelets administrated with IL-17. Moreover,the levels of aggregation,CD62 P,PAC-1,P53 and the phosphorylation of ERK2 were enhanced along with the MPTP opening in platelets pre-stimulated with IL-17. However,Cs A attenuated these effects triggered by IL-17. It was suggested that IL-17 could induce MPTP opening through ERK2 and P53 signaling pathway in platelet activation and aggregation.展开更多
Objective: To study the gene mutations of homeobox transcription factor ( CSX /NKX2.5) associated with a Chinese familywith secundum atrial septal defect ( ASD) . Methods: Polymerase chain reaction and DNA sequencing ...Objective: To study the gene mutations of homeobox transcription factor ( CSX /NKX2.5) associated with a Chinese familywith secundum atrial septal defect ( ASD) . Methods: Polymerase chain reaction and DNA sequencing were used to check allthe members in the family with ASD, and single strand conformation polymorphism analysis ( SSCP) was used to check 126normal control people for detecting the mutations of CSX /NKX2.5 gene. Results: Three mutations, G270A( Glu32Lys) , G378A( Glu68Lys) andG390A ( Glu72Lys) were identified in CSX /NKX2.5 gene of ASD patients. However, the other members in thefamily with ASD and the control did not have such gene mutations. Conclusion: These mutations of CSX /NKX2.5 gene,which were identified in a Chinese family, may be one of the secundum ASD etiologic causes.展开更多
Previous investigations have shown that changes in total prostate volume(TPV) are highly variable among aging men,and a considerable proportion of aging men have a stable or decreasing prostate size.Although there is ...Previous investigations have shown that changes in total prostate volume(TPV) are highly variable among aging men,and a considerable proportion of aging men have a stable or decreasing prostate size.Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia,less is known about the appropriate age cut-off points for TPV growth rate.In this community-based cohort study,TPV was examined once a year in men who had consecutive health checkup,during a follow-up of 4 years.A total of 5058 men(age 18–92 years old) were included.We applied multiple regression analyses to estimate the correlation between TPV growth rate and age.Overall,3232(63.9%) men had prostate growth,and 1826(36.1%) had a stable or decreased TPV during the study period.The TPV growth rate was correlated negatively with baseline TPV(r= –0.32,P<0.001).Among 2620 men with baseline TPV <15 cm3,the TPV growth rate increased with age(β=0.98,95% CI:0.77%–1.18%) only up to 53 years old.Among 2188 men with baseline TPV of 15–33.6 cm3,the TPV growth rate increased with age(β=0.84,95% CI,0.66%–1.01%) only up to 61 years old after adjusting for factors of hypertension,obesity,baseline TPV,diabetes mellitus and dyslipidemia.In this longitudinal study,the TPV growth rate increased negatively with baseline TPV,only extending to a certain age and not beyond.Further research is needed to identify the mechanism underlying such differences in prostate growth.展开更多
In order to explore the possible roles played by the autoimmune mechanism in the progression of myocarditis into dilated cardiomyopathy (DCM) using an animal model, we investigated whether autoimmune myocarditis might...In order to explore the possible roles played by the autoimmune mechanism in the progression of myocarditis into dilated cardiomyopathy (DCM) using an animal model, we investigated whether autoimmune myocarditis might develop into DCM Methods Experimental Balb/C mice (n=20) were immunized with cardiac myosin with Freun d’s complete adjuvant at days 0, 7 and 30 The control Balb/C mice (n=10) were immunized with Freund’s complete adjuvant in the same mannere Serum and my ocardium samples were collected after the first immunization at days 15, 21 and 120 The anti-myosin antibody was examined by enzyme-linked immunosorbent assay and immunoblotting Results Pathological findings demonstrated that there was myocardial necrosis or inflammatory infiltration during acute stages and fibrosis mainly in the late phase of experimental group, but the myocardial lesions were not found in the control group Autoimmunity could induce myocarditis and DCM in the absence of viral infection High titer anti-myosin IgG antibodies were found in the experimental group, but not in the control group Furthermore, the anti-myosin heavy chain (200 KD) antibody was positive in 21 of 48 patients with DCM and viral myocarditis, but only 4 of 20 patients with coronary heart disease, including 1 case and 3 c ases that reacted with heavy and light chains (27 5 KD), respectively The antibodies were not detected in healthy donors Conclusion Cardiac myosin might be an autoantigen that provokes autoimmunity and leads to the transformation of myocarditis into DCM Detection of anti-myosin heavy chain antibody might contribute to diagnosis for DCM and viral展开更多
MicroRNAs(miRNAs)are a novel class of small,non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases.Immune cells,especially T helper(Th)cells,are critical in the development of at...MicroRNAs(miRNAs)are a novel class of small,non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases.Immune cells,especially T helper(Th)cells,are critical in the development of atherosclerosis and the onset of acute coronary syndrome(ACS).To assess whether inflammation-related miRNAs(such as miR-155,146a,21,125a-5p,125b,31)are involved in the imbalance of Th cell subsets in patients with ACS,we measured the expression of related miRNAs in patients with acute myocardial infarction(AMI),unstable angina(UA),stable angina(SA)and chest pain syndrome(CPS);analyzed the relationship between miRNA expression and the frequency of Th cell subsets;and observed the co-expression of miR-155 and IL-17A in peripheral blood mononuclear cells(PBMCs)of patients with ACS.The results showed that the expression of miR-155 in the PBMCs of patients with ACS was decreased by approximately 60%,while the expression of both miR-21 and miR-146a was increased by approximately twofold.The expression patterns of miRNAs in plasma correlated with those in PBMCs,except for miR-21,which was increased by approximately sixfold in the AMI group and showed no significant difference between the UA group and the CPS group.We also found that the expression of miR-155 inversely correlated with the frequency of Th17 cells(r520.896,P,0.01)and that miR-155 was co-expressed with IL-17A in patients with ACS.In conclusion,our study revealed the expression patterns of inflammation-related miRNAs in patients with ACS and found that miR-155 may be associated with Th17 cell differentiation.展开更多
Agonistic AT1 receptor autoantibodies (AT1-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT1-AAs were highly associated with refractory hypertension. Function of vas...Agonistic AT1 receptor autoantibodies (AT1-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT1-AAs were highly associated with refractory hypertension. Function of vascular smooth muscle cells (VSMCs) is important in the regulation of blood pressure. We investigated and compared the ability of angiotensin II (Ang II) and AT1-AAs to stimulate the intracellular calcium mobilization and cellular proliferation of rat VSMCs. Twenty-two patients with refractory hypertension, 24 patients with non-refractory hypertension and 37 normotensives were recruited. The serum of each patient was detected for the presence of AT1-AAs by ELISA. Ang II and the AT1-AAs from the sera of patients were used to stimulate rat VSMCs in vitro. AT1-AAs were detected in 10/22, 3/24 and 3/37 of patients with refractory hypertension, non-refractory hypertension and normotensives, respectively. AT1-AAs led the increase intracellular calcium mobilization in a dose-dependent manner and cellular proliferation of VSMCs just as Ang II. Both of these effects caused by AT1-AAs were blocked with losartan or a peptide corresponding to a part of the second extracellular loop of AT1 receptor. Since AT1-AAs exhibited pharmacological activity in rat VSMCs just as Ang II, they might play a role in the elevation of peripheral vascular resistance and in vascular remodeling. And AT1-AAs were suggested to involve in resistance to antihypertensive therapy.展开更多
文摘Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE-/-mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as com-pared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a signifi-cant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-βantibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.
基金the National Natural Sciences Foundation of China (No. 30770881)the National Basic Research Program of China (973 Program) (No. 2007CB512000)
文摘In ischemic hypertrophic myocardium, contractile dysfunction can be attributed to the decreased calcium induced calcium release (CICR) in cytoplasm. This study aimed to investigate the electrophysiological properties and the expression of L calcium channel subunits in post-MI myocardium. The ischemic heart remodeling model was established in SD rats. The expressions of calcium channel subunits were determined by realtime RT-PCR. Whole cell patch clamp was used to record the electrophysiological properties of L calcium channel. The results showed that the L calcium channel agonist Bayk 8644 induced the significantly decreased CICR in the rat cardiomyocyte 6 weeks after myocardial infarction (MI). In the post-MI cardiomyocytes, the amplitude of ICaL decreased dramatically and the inactivation curve of the current shifted to more negative potential. At mRNA level, the expression of the calcium channel alpha1c, beta2c subunits decreased dramatically in the ventricle of post-MI rats. The expression of alpha2/delta subunit, however, remained constant. It is concluded that the abnormal expression of the L calcium channel subunits in post-MI cardiomyocytes contributes to the ICaL decrease at early stage of the ischemic remodeling in cardiomyocytes, which leads to the decreased CICR in the cell and contractile dysfunction of myocardium.
基金the National Natural Science Foundation of China(Nos.81701653 and 81570348).
文摘Myocardial fiber deformation measurements have been reported to be associated with adverse outcomes in patients with acute heart failure and those with myocardial infarction.However,few studies have addressed the prognostic value of global circumferential strain(GCS)in dilated cardiomyopathy(DCM)patients with severely impaired systolic function.This study aimed to evaluate the prognostic value of cardiac magnetic resonance(CMR)-derived GCS in DCM patients with severely reduced ejection.Consecutive DCM patients with severely reduced ejection fraction(EF<35%)who underwent CMR were included.GCS was calculated from CMR cine images.The clinical endpoint was a composite of all-cause mortality,heart transplantation,implantable cardioverter defibrillator(ICD)implantation and aborted sudden cardiac death(SCD).A total of 129 patients with a mean EF of 15.33%(11.36%–22.27%)were included.During a median follow-up of 518 days,endpoint events occurred in 50 patients.Patients with GCS≥the median(−5.17%)had significantly reduced event-free survival as compared with those with GCS<the median(P<0.01).GCS was independently associated with adverse events after adjusting for clinical and imaging risk factors including extent of late gadolinium enhancement(LGE)(P<0.05).Adding GCS into the model including the extent of LGE resulted in significant improvements in the C-statistic(from 0.706 to 0.742;P<0.05)with a continuous net reclassification improvement(NRI)of 29.71%.It was concluded that GCS derived from CMR could be useful for risk stratification in DCM patients with severely reduced EF,which may increase common imaging risk factors including LGE.
基金supported by National Natural Science Foundation of China (No. 30871069)
文摘The antibody against AT1-EC2 plays a role in some kinds of inflammatory vascular diseases including malignant hypertension,preeclampsia,and renal-allograft rejection,but the detailed mechanisms remain unclear.In order to investigate the changes of NADPH oxidase and reactive oxygen species in the aorta in a mouse model which can produce AT1-EC2 antibody by active immunization with AT1-EC2 peptide,15 mice were divided into three groups:control group,AT1-EC2-immunized group,and AT1-EC2-immunized and valsartan-treated group.In AT1-EC2-immunized group and AT1-EC2-immunized and valsartan-treated group,the mice were immunized by 50 μg peptide subcutaneously at multiple points for 4 times:0,5,10,and 15 days after the experiment.In AT1-EC2-immunized and valsartan-treated group,valsartan was given at a dose of 100 mg/kg every day for 20 days.After the experiment,the mice were sacrificed under anesthesia and the aortas were obtained and frozen in liquid nitrogen for the preparation of frozen section slides and other experiments.The titer of AT1-EC2 was assayed by using ELISA.The level of NOX1 mRNA in the aorta was determined by using RT-PCR.The expression of NOX1 was detected by using Western blotting.Confocal scanning microscopy was used to assay the α-actin and NOX1 expression in the aortic tissue.The O 2.production was detected in situ after DHE staining.The mice produced high level antibody against AT1-EC2 in AT1-EC2-immunized group and AT1-EC2-immunized and valsartan-treated group,and the level of NOX1 mRNA in the aortic tissues was 1.6±0.4 times higher and the NOX1 protein expression was higher in AT1-EC2-immunized group than in control group.There were no significant differences in the level of NOX1 mRNA and protein expression between control group and AT1-EC2-immunized and valsartan-treated group.The expression and co-localization of α-actin and NOX1 in AT1-EC2-immunized group increased significantly as compared with those in control group,and the O 2.production increased about 2.7 times as compared with control group.There were no significant differences between control group and AT1-EC2-immunized and valsartan-treated group.It is concluded that active immunization with AT1-EC2 can activate NOX1-ROS,and increase vascular inflammation,which can be inhibited by AT1 receptor blocker valsartan.This may partially explain the mechanism of the pathogenesis of inflammatory vascular diseases related to antibody against AT1-EC2.
基金This work was supported by the National Natural Science Foundation of China (No.81370263 and No.81500348).
文摘Poly(ADP-ribose) polymerase 1 (PARP1) plays important roles in the regulation of transcription factors. Mounting evidence has shown that inhibition of PARP1 influences the expression of genes associated with inflammatory response. Interferon regulatory factor 1 (IRF1) is a critical transcription factor for the development of both the innate and adaptive immune responses against infections. However, the molecular mechanism through which PARP1 mediates the effects has not been clearly demonstrated. Jurkat cells were exposed to dexamethasone (Dex) or PARP1 inhibitor PJ34. The expression levels of IL-12, LMP2, OAS1 and PKR were detected using real-time RT-PCR. The interactions between PARP1 and IRF1 were examined by coimmunoprecipitation (co-IP) assays. We further explored the mechanism of PARP1 suppressing IRF1 by assessing the activities of interferon stimulated response element (ISRE). The mRNA expression of IL-12, LMP2, OAS1 and PKR was obviously suppressed by Dex in Jurkat cells, which could be rescued by PJ34 treatment. Luciferase study revealed that poly(ADP-ribosyl)- ation suppressed IRF1-mediated transcription through preventing the binding of IRF1 to ISREs. PARP1 inhibited IRF1-mediated transcription in Jurkat cells by preventing IRF1 binding to ISREs in the promoters of target genes. It is suggested that PARP1 is a crucial regulator of IRF1-mediated immune response. This study provides experimental evidence for the possible application of PARP1 inhibitors in the treatment of IRF1-related immune anergy.
基金This project was supported by a grant from National Natu-ral Sciences Foundation of China (No. 30370574)
文摘To observe the dynamic changes of the TGF-β1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively. The relative levels of mRNA of TGF-β1, collagen type Ⅰ, Ⅲ, and fetal gene beta-MHC were de- tected by RT-PCR. The distribution of TGF-β1 protein in the myocardium was detected by immuno- histochemistry. The results showed that the size of infarction was higher than that of the sham oper- ated groups in the infarcted group (44.5±0.5 vs 0). The difference in hemodynamic parameters be- tween the infarcted group and sham operated group was significant (P<0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day, which lasted 4 weeks. Then, it decreased gradually. β-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type Ⅰ /Ⅲ showed similar changes as compared with the sham operated groups (P<0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P<0.01) at day 180. Linear regression analysis indicated that the TGF-β1 was posi- tively correlated with the ventricular remodeling.It was concluded that the cytokine TGF-β1 par- ticipates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.
文摘Objective: To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation (A/R) injury of neonatal rat. Methods:The model of A/R injury was finished through receiving anoxia for 2 h and reoxygenation for 4 h in cultured cardiomyocytes of neonatal rat. The cardiomyocytes were divided randomly into 3 groups: control group (CON), anoxia/reoxygenation group (A/R) and insulin-treated group (INS). At the end of reoxygenation of 4 hours, activities of lactate dehydrogenase (LDH), contents of malondialdehyde (MDA) were assessed through spectrophotometric procedures, myocyte apoptosis were detected through TUNEL and DNA Ladder. Results: MDA, LDH, and Apoptosis Index were significantly decreased in INS group compared with A/R group (P<0.01). Conclusion: Insulin has a protective effect against A/R injury in cultured cardiomyocyte of neonatal rat; the protective mechanism may contribute to antiapoptosis of insulin.
基金the National Basic Research Program of China (973 Program) (No. 2007CB512000, 2007CB512005)National Natural Science Foundation of China (No. 30600234)
文摘The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class Ⅱ and CD86. Supernatants were analyzed for the production of IL-12 and IFN-γ cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-γ production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.
基金This project was supported by a grant from National Natu-ral Sciences Foundation of China (No .39970306) .
文摘In order to study the expression of IL-1β and TNF-α in the myocardium of MCMV myocarditis and their role in the myocardial damages, 60 BALB/C mice of 4 weeks were randomly divided into two groups: 36 were injected intraperitoneally with MCMV and 24 served as control group. Immunohistochemistry was used to detect IL-1β and TNF-α expression in the myocardium, and myocardial lesions were observed histopathologically. Histopathological study on the myocardium from infected mice revealed focal or diffuse lesions characterized by inflammatory cells and degeneration or necrosis of myocytes. The myocardial lesion score showed the degree of inflammatory cell infiltration was slight in MCMV myocarditis.The positive staining signals for IL-1β and TNF-α proteins which mainly located in the infiltrating inflammatory cells and degenerative or necrotic myocytes were markedly detectable whereas there were no positive findings in the myocardium of control mice. IL-1β and TNF-α was expressed in the myocardium of viral myocarditis murine model induced by MCMV. IL-1β and TNF-α may play an important role in the pathogenesis of viral myocarditis.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30600574)
文摘Autonomic nervous system activation can result in significant changes of atrial electrophysiology and facilitate induction of atrial fibrillation. By recording influence of different concentrations of acetylcholine (ACh) on atrial fibers (AF), we investigated the role of the increased vagal tone in electrical remodeling in atrial fibrillation. Parameters of action potentials and force contraction (Fc) in atrial fibers were recorded by using standard intracellular microelectrode technique and force transducer. It was found that: (1) ACh at 0.1 μmol/L had no significant influence on spontaneous action potentials (SAPs) and Fc (n=6, P>0.05); ACh at both 1.0 and 10.0 μmol/L shortened action potential duration (APD) and Fc of human AF from right atrium (n=6, P<0.05); there was no significant difference in shortening APD between 10.0 and 1.0 μmol/L of ACh; (2) ACh at 0.1 μmol/L had no significant desensitization (n=6, P>0.05), but ACh at 1.0 and 10.0 μmol/L had desensitization (n=6, P<0.05) to SAPs and Fc. The desensitization of ACh on APD in AF was concentration- and time-dependent. It was shown that APD was longer than the control along with extending time of continuous Tyrode's solution perfusion after desensitization. It is concluded that ACh changes the electrophysiological characteristics of human AF, indicating that increased vagal tone plays a role in the development of a vulnerable substrate for atrial electrical remodeling in atrial fibrillation.
基金supported by the National Natural Science Foundation of China(No.81370324)
文摘Regulatory T cells(Tregs) play a pivotal role in the pathological development of hypertension.Helios,a transcription factor from the Ikaros family,was recently reported to be a bona fide marker for natural Tregs or activated Tregs with suppression function,however,little has been known about its role in hypertension.This study was aimed to find whether Helios+ Tregs really play a vital role in hypertension.A total of 60 hypertension patients,and 46 normotension subjects were enrolled in this study.Frequencies of different Tregs subsets in peripheral blood were measured by flow cytometry.Plasma cytokine level was determined by ELISA.The m RNA expression of Foxp3 and Helios in purified CD4+ T cells was detected by RT-PCR.Proportion of CD4+Foxp3+Helios+ Tregs was decreased significantly in patients with hypertension(62.52%±1.18% vs.71.89%±1.03%,P<0.01),and it was correlated with plasma level of IL-10 positively(r=0.505,P<0.05) and plasma level of IFN-gamma negatively(r=–0.551,P<0.05).The m RNA expression of Foxp3(7.23±1.00 vs.10.58±0.54,P<0.05) and Helios(8.47±0.95 vs.15.52±2.0,P<0.05) was decreased in CD4+ T cells from patients with hypertension.Helios+ Tregs were decreased in patients with hypertension and may play a protective role in hypertension progression.
基金the National Natural Science Foundation of China (No. 30000070)
文摘The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6–8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-γ and IL-4 of Th cells were moni- tored with flow cytometry, and splenic T cell cytokines IFN-γ, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P<0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P<0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.
文摘Objectives To study the depressive effect of the antisense oligonuceotides (ASODN) of c-myc and proliferating cell nuclear antigen (PCNA) on the proliferation of VSMC. Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4～8 generation as research object. The objects were divided into three groups to carry out control study: control group, PCNA ASODN group and c-myc ASODN group. The ASODNs' working concentration all were 1:50. The depressive effect of ASODN on VSMC proliferation was investigated by cell counting, MTT and 3H-TdR incorporation assay; PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA and c-myc ASODN into VSMC. Results PCNA and c-myc ASODN could inhibit the proliferation of VSMC significantly, compared with control group (P<0.05). ② Transferring PCNA and c-myc ASODN into VSMC obtained successfully; the corresponding gene was inhibited obviously; compared with control group (P<0.05). Conclusions PCNA and c-myc might play a considerable role in the VSMC proliferation process. The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC, and then the proliferation of VSMC was slowed down. This study presented a beneficial proposal and theoretical fundament for atherosclerotic treatment.
基金supported by the National Natural Science Foundation of China(Nos.81370425,81470502,and 81400283)
文摘The opening of mitochondrial permeability transition pore(MPTP) plays a critical role in platelet activation. However,the potential trigger of the MPTP opening in platelet activation remains unknown. Inflammation is the crucial trigger of platelet activation. In this study,we aimed to explore whether and how the important inflammatory cytokine IL-17 is associated with MPTP opening in platelets activation by using MPTP inhibitor cyclosporine-A(Cs A). The mitochondrial membrane potential(Δψm) was detected to reflect MPTP opening levels. And the platelet aggregation,activation,and the primary signaling pathway were also tested. The results showed that the MPTP opening levels were increased and Δψm reduced in platelets administrated with IL-17. Moreover,the levels of aggregation,CD62 P,PAC-1,P53 and the phosphorylation of ERK2 were enhanced along with the MPTP opening in platelets pre-stimulated with IL-17. However,Cs A attenuated these effects triggered by IL-17. It was suggested that IL-17 could induce MPTP opening through ERK2 and P53 signaling pathway in platelet activation and aggregation.
文摘Objective: To study the gene mutations of homeobox transcription factor ( CSX /NKX2.5) associated with a Chinese familywith secundum atrial septal defect ( ASD) . Methods: Polymerase chain reaction and DNA sequencing were used to check allthe members in the family with ASD, and single strand conformation polymorphism analysis ( SSCP) was used to check 126normal control people for detecting the mutations of CSX /NKX2.5 gene. Results: Three mutations, G270A( Glu32Lys) , G378A( Glu68Lys) andG390A ( Glu72Lys) were identified in CSX /NKX2.5 gene of ASD patients. However, the other members in thefamily with ASD and the control did not have such gene mutations. Conclusion: These mutations of CSX /NKX2.5 gene,which were identified in a Chinese family, may be one of the secundum ASD etiologic causes.
基金supported by National Natural Science Foundation of China(No.81370468)
文摘Previous investigations have shown that changes in total prostate volume(TPV) are highly variable among aging men,and a considerable proportion of aging men have a stable or decreasing prostate size.Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia,less is known about the appropriate age cut-off points for TPV growth rate.In this community-based cohort study,TPV was examined once a year in men who had consecutive health checkup,during a follow-up of 4 years.A total of 5058 men(age 18–92 years old) were included.We applied multiple regression analyses to estimate the correlation between TPV growth rate and age.Overall,3232(63.9%) men had prostate growth,and 1826(36.1%) had a stable or decreased TPV during the study period.The TPV growth rate was correlated negatively with baseline TPV(r= –0.32,P<0.001).Among 2620 men with baseline TPV <15 cm3,the TPV growth rate increased with age(β=0.98,95% CI:0.77%–1.18%) only up to 53 years old.Among 2188 men with baseline TPV of 15–33.6 cm3,the TPV growth rate increased with age(β=0.84,95% CI,0.66%–1.01%) only up to 61 years old after adjusting for factors of hypertension,obesity,baseline TPV,diabetes mellitus and dyslipidemia.In this longitudinal study,the TPV growth rate increased negatively with baseline TPV,only extending to a certain age and not beyond.Further research is needed to identify the mechanism underlying such differences in prostate growth.
文摘In order to explore the possible roles played by the autoimmune mechanism in the progression of myocarditis into dilated cardiomyopathy (DCM) using an animal model, we investigated whether autoimmune myocarditis might develop into DCM Methods Experimental Balb/C mice (n=20) were immunized with cardiac myosin with Freun d’s complete adjuvant at days 0, 7 and 30 The control Balb/C mice (n=10) were immunized with Freund’s complete adjuvant in the same mannere Serum and my ocardium samples were collected after the first immunization at days 15, 21 and 120 The anti-myosin antibody was examined by enzyme-linked immunosorbent assay and immunoblotting Results Pathological findings demonstrated that there was myocardial necrosis or inflammatory infiltration during acute stages and fibrosis mainly in the late phase of experimental group, but the myocardial lesions were not found in the control group Autoimmunity could induce myocarditis and DCM in the absence of viral infection High titer anti-myosin IgG antibodies were found in the experimental group, but not in the control group Furthermore, the anti-myosin heavy chain (200 KD) antibody was positive in 21 of 48 patients with DCM and viral myocarditis, but only 4 of 20 patients with coronary heart disease, including 1 case and 3 c ases that reacted with heavy and light chains (27 5 KD), respectively The antibodies were not detected in healthy donors Conclusion Cardiac myosin might be an autoantigen that provokes autoimmunity and leads to the transformation of myocarditis into DCM Detection of anti-myosin heavy chain antibody might contribute to diagnosis for DCM and viral
基金supported by the National Natural Science Foundation of China(no.81000085)the Doctor and Novo-teacher Foundation of Chinese National Ministry of Education(no.20090142120049).
文摘MicroRNAs(miRNAs)are a novel class of small,non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases.Immune cells,especially T helper(Th)cells,are critical in the development of atherosclerosis and the onset of acute coronary syndrome(ACS).To assess whether inflammation-related miRNAs(such as miR-155,146a,21,125a-5p,125b,31)are involved in the imbalance of Th cell subsets in patients with ACS,we measured the expression of related miRNAs in patients with acute myocardial infarction(AMI),unstable angina(UA),stable angina(SA)and chest pain syndrome(CPS);analyzed the relationship between miRNA expression and the frequency of Th cell subsets;and observed the co-expression of miR-155 and IL-17A in peripheral blood mononuclear cells(PBMCs)of patients with ACS.The results showed that the expression of miR-155 in the PBMCs of patients with ACS was decreased by approximately 60%,while the expression of both miR-21 and miR-146a was increased by approximately twofold.The expression patterns of miRNAs in plasma correlated with those in PBMCs,except for miR-21,which was increased by approximately sixfold in the AMI group and showed no significant difference between the UA group and the CPS group.We also found that the expression of miR-155 inversely correlated with the frequency of Th17 cells(r520.896,P,0.01)and that miR-155 was co-expressed with IL-17A in patients with ACS.In conclusion,our study revealed the expression patterns of inflammation-related miRNAs in patients with ACS and found that miR-155 may be associated with Th17 cell differentiation.
基金This work was funded by National Natural Science Foundation of China(Project No.30300133 and Project No.30600235).
文摘Agonistic AT1 receptor autoantibodies (AT1-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT1-AAs were highly associated with refractory hypertension. Function of vascular smooth muscle cells (VSMCs) is important in the regulation of blood pressure. We investigated and compared the ability of angiotensin II (Ang II) and AT1-AAs to stimulate the intracellular calcium mobilization and cellular proliferation of rat VSMCs. Twenty-two patients with refractory hypertension, 24 patients with non-refractory hypertension and 37 normotensives were recruited. The serum of each patient was detected for the presence of AT1-AAs by ELISA. Ang II and the AT1-AAs from the sera of patients were used to stimulate rat VSMCs in vitro. AT1-AAs were detected in 10/22, 3/24 and 3/37 of patients with refractory hypertension, non-refractory hypertension and normotensives, respectively. AT1-AAs led the increase intracellular calcium mobilization in a dose-dependent manner and cellular proliferation of VSMCs just as Ang II. Both of these effects caused by AT1-AAs were blocked with losartan or a peptide corresponding to a part of the second extracellular loop of AT1 receptor. Since AT1-AAs exhibited pharmacological activity in rat VSMCs just as Ang II, they might play a role in the elevation of peripheral vascular resistance and in vascular remodeling. And AT1-AAs were suggested to involve in resistance to antihypertensive therapy.
