Objective:By the method of network pharmacology to study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of Coronary Microvascu...Objective:By the method of network pharmacology to study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction(CMD).Methods:Obtaining potential active compounds of Chenpi-Banxia from TCMSP,while the targets for CMD were obtained from DrugBank and OMIM databases.Using UniProt database to query the corresponding gene name.The key target of Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction can be obtained by using the intersection of VENNY.The PPI network was screened for the major targets by String and Cytoscape3.7.1.The GO enrichment analysis and KEGG Pathway analyses of major targets were performed by using the DAVID database and use Binformatics to draw bubble map.Finally,the ingredient-major arget-key pathway network was constructed by Cytoscape3.7.1.Results:There were 16 compounds such as naringenin,nobiletin,baicalein.beta-sitosterol etc,and 56 predictive target genes such as AKT1、VEGFA、BCL2、BAX、JUN etc,as well as 20 key pathways including inflammation-related pathway(TNF signaling pathway),pathways related to cardiovascular system(PI3K-Akt signaling pathway),Vascular endothelial growth factor signaling pathway(VEGF signaling pathway),Apoptosis related pathways(Apoptosis)and Hypoxia cell stress signaling pathway(HIF-1 signaling pathway)in the Compounds-Target-Pathway network.Conclusion:The study verified the characteristics of multi-components,multi-targets and integral regulation for Chenpi-Banxia with the application of network pharmacology.It predicted that Chenpi-Banxia couldtreat Coronary Microvascular Dysfunction mainly by protecting endothelial cell function of coronary microcirculation,inhibiting cell apoptosis and affecting inflammatory reaction.展开更多
The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arter...The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arteries.These data are confirmed in diabetic animal mod-els,where lesions of small coronary arteries have been described.These concepts are epitomized in the classic microvascular complications of diabetes,i.e.blindness,kidney failure and distal dry gangrene.Most importantly,accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility.This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes,and assesses the current state of knowledge regarding the triggers for inflammation in this disease.We evaluate the roles of hyperglycemia,oxidative stress,polyol pathway,protein kinase C,advanced glycation end products,insulin resistance,peroxisome proliferator-activated receptor-γ,inflammation,and diabetic cardiomyopathy as a "stem cell disease".Furthermore,we discuss the mechanisms responsible for impaired coronary arteriole function.Finally,we consider how new insights in diabetes may provide innovative therapeutic strategies.展开更多
Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary micro...Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation,but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography(MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction,respectively,and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall,MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice,but the approval of regulatory authorities is lacking.展开更多
The present study aims to determine the influence of microvascular dysfunction (MVD) in the prognosis of patients presenting isolated left bundle branch block (LBBB). Methods: We studied 30 patients (pts), 22 males, 8...The present study aims to determine the influence of microvascular dysfunction (MVD) in the prognosis of patients presenting isolated left bundle branch block (LBBB). Methods: We studied 30 patients (pts), 22 males, 8 females, mean age 57 ± 4 years, with isolated LBBB, with a mean follow up of 48 ± 6 months. The control group consisted of 20 healthy individuals, 12 males, mean age 52 ± 10 years. Both groups were screened for cardiovascular risk factors (RF);they also had an echocardiogram and Coronary CT Scan, ruling out both structural heart disease and obstructive lesions of the epicardial coronary arteries. A myocardial perfusion study was then performed, with two groups emerging according to these results: Group A, 8 pts (26%), with reversible perfusion defects, in which the diagnosis of MVD was suspected, and Group B, 22 pts (74%), with either normal perfusion or minor septal/apical reversible defects (related to LBBB). All Group A pts, and 9 of the Group B pts, underwent coronary arteriography, with intracoronary acetylcholine and nitroglycerine infusion, thus evaluating vasomotor response as endothelium dependent (acetylcholine) or endothelium independent (nitroglycerine). During follow up, we reviewed functional class, 12 lead ECG and echocardiogram on a yearly basis. Results: All Group A patients had an abnormal acetylcholine response;only three of them had abnormal response to nitroglycerine infusion, suggesting endothelium dependent MVD. Of those in Group B, only one patient had abnormal acetylcholine response. At the end of the follow up period, 3 pts (37%) in Group A, showed functional class decrease vs 5 pts (22%) of those in Group B. In Group A, a significant increase of End Diastolic Left Ventricle Diameter (EDLVD) was found (51.6 ± 3.6 vs 59.3 ± 6.8 mm;p < 0.05) with significant decrease in LVEF (62 ± 4.8 vs 46% ± 3.7%, p variation. In neither group major complications (death, heart failure admissions) were found. Conclusion: We confirm the association between MVD and a worse clinical prognosis in isolated LBBB patients. Repeated ischemia and myocardial fibrosis are highlighted as possible physiopathological mechanisms, precluding a progressive left ventricular function decrease, with a higher mortality and arrhythmia risk. Endothelial function preserving strategies, both preventive and therapeutic, might be useful in improving LBBB with MVD patient’s prognosis.展开更多
Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).T...Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.展开更多
The management of dilated cardiomyopathy(DCM) is well established. However, a subset of patients does not have recovery from or have recurrences of left ventricular(LV) dysfunction despite receiving optimal medical th...The management of dilated cardiomyopathy(DCM) is well established. However, a subset of patients does not have recovery from or have recurrences of left ventricular(LV) dysfunction despite receiving optimal medical therapy. Coronary microvascular dysfunction(CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. Dilated myocardial phenotype may be responsible for CMD in DCM. Anisodamine can exert a significant effect on relieving microvascular spasm, and improving and dredging the coronary microcirculation. However,whether CMD can be potentially improved with anisodamine to make DCM better remains incompletely understood.展开更多
AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biolog...AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.展开更多
AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaertn, has been clinically used for vascular diseases such as occlusive v...AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaertn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, SaMae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation.Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/reperfusion (I/R) in rats fed ethanol chronically.METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 rain of gut ischemia followed by 60 rain of reperfusion.Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 rain after the onset of superior mesenteric artery ocdusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion.Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia.RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats,the gut I/R-induced increases in the number of stationary leukooltes, plasma endotoxin levels and ALT activities were enhanced. Pretreat^nent with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption.CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.展开更多
Background Cathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis,especially in the plaque destabilization and rupture leading to acute coronary syndrome.However, whe...Background Cathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis,especially in the plaque destabilization and rupture leading to acute coronary syndrome.However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet. Methods Sprague-Dawley rats were randomly divided into three groups;Sham group,CME group and SB203580 group (n=10 per group).CME rats were produced by injection of 42μm microspheres into the left ventricle with occlusion of the ascending aorta.SB203580,a p38 MAPK inhibitor,was injected into femoral vein after finishing the injection of microspheres in SB203580 group.Left ventricular Ejection Fraction was determined by echocardiography.The level of phosphorylated and total P38 MAPK in myocardium was assessed by Western Blot.Results Left ventricular(LV) Ejection Fraction was depressed at 3 hours and until up to 12 hours in CME group.The increased p38 MAPK activation was observed in CME group.The administration of SB203580 partly inhibited the p38 MAPK activity and preserved cardiac contractile function.Conclusions p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly preserve cardiac contractile function.展开更多
Propylene glycol alginate sodium sulfate-loaded nanoparticles(PSS-NP) has been shown potential to prevent the microvascular endothelial injuries caused by diabetic cardiomyopathy(DCM). In this study, we aimed to inves...Propylene glycol alginate sodium sulfate-loaded nanoparticles(PSS-NP) has been shown potential to prevent the microvascular endothelial injuries caused by diabetic cardiomyopathy(DCM). In this study, we aimed to investigate the effects of PSS-NP on the dysfunction of cardiac microvascular endothelia in streptozotocin(STZ)-induced DCM rat model. Echocardiographic measurements showed a significant improvement of cardiac function in the PSS-NP-treated group. Our results revealed that the abnormalities of cardiac systolic and diastolic functions were suppressed by the treatments of prostaglandin E1(PGE1), low molecular weight heparin(LMWH), PSS and PSS-NP. Our comparison analysis indicated that PSS-NP showed the strongest inhibitory effects on microvascular endothelial injuries. Transmission electron microscopy analysis demonstrated that PSS-NP protected the cardiac microvascular endothelium and further improved endothelium dysfunction in DCM rats. ELISA and Western blot assays further showed a high efficiency of improving cardiac microvascular endothelial dysfunction with PSS-NP. Our results demonstrated that PSS-NP increased the protein expression of phosphatidylinositol 3-kinase(PI3K)-p85 and vascular endothelial growth factor(VEGF)-A, and the phosphorylation of protein kinase B(Akt) and endothelial nitric oxide synthase(eNOS), which were involved in the amelioration of cardiac microvascular endothelial dysfunction. These data suggest that PSS-NP may be a novel approach to the treatment the coronary microcirculation disorder diseases such as DCM.展开更多
The incidence of both atrial fibrillation(AF)and coronary artery disease(CAD)increases with advancing age.They share common risk factors and very often coexist.Evidence points to an intricate relationship between atri...The incidence of both atrial fibrillation(AF)and coronary artery disease(CAD)increases with advancing age.They share common risk factors and very often coexist.Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level.In this review,we delineated this complex relationship,identified a common theme between the two,and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management.Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography.Further,the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship.CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity.AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system.In a nutshell,the two form a vicious cycle wherein one disease promotes the other.Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism.Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients.Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases.The relationship between AF and CAD is complex and much more than mere coincidence.The two diseases share common risk factor and pathophysiology.Hence,it is impractical to treat them in isolation.Accordingly,we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.展开更多
Patients with ischemic cardiomyopathy constitute a heterogeneous group of patients with an extremely complex condition in which many factors play an important prognostic role. So it is difficult and probably unrealist...Patients with ischemic cardiomyopathy constitute a heterogeneous group of patients with an extremely complex condition in which many factors play an important prognostic role. So it is difficult and probably unrealistic to expect that a single feature like presence of viable myocardium would provide an unequivocal answer to a critical question of revasculrization or not for all patients. Opposite to the hopes of investigators and physicians involved in the care of these patients, the findings of prospective studies with the use of different viability testing methods did not help in the decision-making process regarding CABG in ischemic cardiomyopathy. Instead, they left us with the same dilemma. The implication of most of these trials is that in patients with CAD and significant LV dysfunction, assessment of myocardial viability does not identify patients who will have the greatest survival benefit from adding CABG to aggressive medical therapy. In the clinical practice, these observations remind physicians to consider the multiplicity of factors involved in the decision-making process for patients with such a complex disease.展开更多
Background: The intra-aortic balloon pumping (IABP) is the most used ventricular mechanical assist device. In recent years, the preoperative use in patients with severe ventricular dysfunction presents itself as a gre...Background: The intra-aortic balloon pumping (IABP) is the most used ventricular mechanical assist device. In recent years, the preoperative use in patients with severe ventricular dysfunction presents itself as a great benefic strategy to the postoperative recovery. This paper aim is to evaluate the IABP post-operative benefit in patients with severe ventricular dysfunction. Methods: From January 2011 to March 2016, 125 patients underwent a coronary artery bypass graft (CABG) with cardiopulmonary bypass and preoperative IABP in Teaching Hospital of the ABC Medical School and Hospital Estadual Mario Covas. The inclusion criteria were the presence of severe ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) less than or equal to 40%, estimated by Doppler echocardiography using the Simpson method. The preoperative LVEF was 30.25% ± 8.53% and the diastolic diameter of the left ventricle (LVDD) 67.75 ± 16.37 mm. IABP was installed approximately 15 hours before the surgery. Results: The patients required the IABP for 2.4 ± 1.58 days, and vasoactive drugs, 4.8 ± 2.12 days. We performed 3.2 ± 1.9 grafts per patient and the total length of stay was 07 ± 5.52 days. Cardiopulmonary bypass time was 67 ± 10.95 minutes and anoxia time, 46.4 ± 10.06 minutes. Twelve patients (9.6%) had pneumonia and four (3.2%), atrial fibrillation. We observed a LVDD reduction to 63 ± 16.26 (p = 0.068) and LVEF enhancement to 36.50 ± 16.86 (p = 0.144). The data were analyzed statistically according to the Wilcoxon test. There were no deaths. Conclusion: The initial experience of the authors with the preoperative IABP in patients with severe left ventricular dysfunction suggests great benefit in post-operative recovery with im-provement of LVEF and reduction of LVDD.展开更多
Objectives To evaluate the relationship of renal dysfunction,coronary heart disease and percutaneous coronary intervention(PCI).Methods(l)The subjects:There were 376 patients who come from department of cardiology of ...Objectives To evaluate the relationship of renal dysfunction,coronary heart disease and percutaneous coronary intervention(PCI).Methods(l)The subjects:There were 376 patients who come from department of cardiology of our hospital in this study undergoing coronary angiography.The patients were divided into two groups? according to coronary angiography:coronary artery disease(group A,n =263),in which 141 patients with renal dysfunction(group A1) and 122 patients with normal renal function(group A2):patients with other kinds of cardiovascular disease but normal coronary angiography(group B.n=113).Before the coronary angiography, all patients were measured the serum creatinine, microalbuminuria,fasting blood-glucose,triglycerides,total cholesterol,high density lipoprotein,low density lipoprotein, blood pressure in fasting 12 hours.(2)The diagnostic criteria for renal dysfunction:male serum creatinine】115 umol/L and/or microalbuminuria】30 mg,female】107 umol/L and/ or】30 mg.Results(1)The differences of renal function indexes in the group A and B:The mean level of microalbuminuria and serum creatinine was higher significantly in group A than that of the group B(43.48±38.93 vs.11.23±7.07 and 101.52±37.22 vs.80.62±17.4 respectively.Conclusions The coronary heart disease patients with renal dysfunction had more severe coronary artery stenosis,The renal dysfunction is a strong and independent risk factors for the coronary heart disease and beeds more revascularization therapy.展开更多
基金National TCM Clinical Research Base Business Construction Research Project of National Administration of Traditional Chinese Medicine(No.JDZX2015033)Liaoning Provincial Science and Technology Fund Project(No.20180530016)Liaoning Provincial Distinguished Professor Program[No.(2017)3]。
文摘Objective:By the method of network pharmacology to study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction(CMD).Methods:Obtaining potential active compounds of Chenpi-Banxia from TCMSP,while the targets for CMD were obtained from DrugBank and OMIM databases.Using UniProt database to query the corresponding gene name.The key target of Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction can be obtained by using the intersection of VENNY.The PPI network was screened for the major targets by String and Cytoscape3.7.1.The GO enrichment analysis and KEGG Pathway analyses of major targets were performed by using the DAVID database and use Binformatics to draw bubble map.Finally,the ingredient-major arget-key pathway network was constructed by Cytoscape3.7.1.Results:There were 16 compounds such as naringenin,nobiletin,baicalein.beta-sitosterol etc,and 56 predictive target genes such as AKT1、VEGFA、BCL2、BAX、JUN etc,as well as 20 key pathways including inflammation-related pathway(TNF signaling pathway),pathways related to cardiovascular system(PI3K-Akt signaling pathway),Vascular endothelial growth factor signaling pathway(VEGF signaling pathway),Apoptosis related pathways(Apoptosis)and Hypoxia cell stress signaling pathway(HIF-1 signaling pathway)in the Compounds-Target-Pathway network.Conclusion:The study verified the characteristics of multi-components,multi-targets and integral regulation for Chenpi-Banxia with the application of network pharmacology.It predicted that Chenpi-Banxia couldtreat Coronary Microvascular Dysfunction mainly by protecting endothelial cell function of coronary microcirculation,inhibiting cell apoptosis and affecting inflammatory reaction.
基金Supported by Grants from Pfizer Atorvastatin Research Award,No. 2004-37American Heart Association SDG,No. 110350047ANIH Grants,No. RO1 HL077566 and RO1 HL085119 to Zhang C
文摘The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arteries.These data are confirmed in diabetic animal mod-els,where lesions of small coronary arteries have been described.These concepts are epitomized in the classic microvascular complications of diabetes,i.e.blindness,kidney failure and distal dry gangrene.Most importantly,accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility.This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes,and assesses the current state of knowledge regarding the triggers for inflammation in this disease.We evaluate the roles of hyperglycemia,oxidative stress,polyol pathway,protein kinase C,advanced glycation end products,insulin resistance,peroxisome proliferator-activated receptor-γ,inflammation,and diabetic cardiomyopathy as a "stem cell disease".Furthermore,we discuss the mechanisms responsible for impaired coronary arteriole function.Finally,we consider how new insights in diabetes may provide innovative therapeutic strategies.
文摘Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation,but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography(MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction,respectively,and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall,MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice,but the approval of regulatory authorities is lacking.
文摘The present study aims to determine the influence of microvascular dysfunction (MVD) in the prognosis of patients presenting isolated left bundle branch block (LBBB). Methods: We studied 30 patients (pts), 22 males, 8 females, mean age 57 ± 4 years, with isolated LBBB, with a mean follow up of 48 ± 6 months. The control group consisted of 20 healthy individuals, 12 males, mean age 52 ± 10 years. Both groups were screened for cardiovascular risk factors (RF);they also had an echocardiogram and Coronary CT Scan, ruling out both structural heart disease and obstructive lesions of the epicardial coronary arteries. A myocardial perfusion study was then performed, with two groups emerging according to these results: Group A, 8 pts (26%), with reversible perfusion defects, in which the diagnosis of MVD was suspected, and Group B, 22 pts (74%), with either normal perfusion or minor septal/apical reversible defects (related to LBBB). All Group A pts, and 9 of the Group B pts, underwent coronary arteriography, with intracoronary acetylcholine and nitroglycerine infusion, thus evaluating vasomotor response as endothelium dependent (acetylcholine) or endothelium independent (nitroglycerine). During follow up, we reviewed functional class, 12 lead ECG and echocardiogram on a yearly basis. Results: All Group A patients had an abnormal acetylcholine response;only three of them had abnormal response to nitroglycerine infusion, suggesting endothelium dependent MVD. Of those in Group B, only one patient had abnormal acetylcholine response. At the end of the follow up period, 3 pts (37%) in Group A, showed functional class decrease vs 5 pts (22%) of those in Group B. In Group A, a significant increase of End Diastolic Left Ventricle Diameter (EDLVD) was found (51.6 ± 3.6 vs 59.3 ± 6.8 mm;p < 0.05) with significant decrease in LVEF (62 ± 4.8 vs 46% ± 3.7%, p variation. In neither group major complications (death, heart failure admissions) were found. Conclusion: We confirm the association between MVD and a worse clinical prognosis in isolated LBBB patients. Repeated ischemia and myocardial fibrosis are highlighted as possible physiopathological mechanisms, precluding a progressive left ventricular function decrease, with a higher mortality and arrhythmia risk. Endothelial function preserving strategies, both preventive and therapeutic, might be useful in improving LBBB with MVD patient’s prognosis.
基金This work was supported by grants from the National Natural Sciences Foundation of China(No.81400177)Natural Science Foundation of Beijing Municipality(No.7154249).
文摘Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.
文摘The management of dilated cardiomyopathy(DCM) is well established. However, a subset of patients does not have recovery from or have recurrences of left ventricular(LV) dysfunction despite receiving optimal medical therapy. Coronary microvascular dysfunction(CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. Dilated myocardial phenotype may be responsible for CMD in DCM. Anisodamine can exert a significant effect on relieving microvascular spasm, and improving and dredging the coronary microcirculation. However,whether CMD can be potentially improved with anisodamine to make DCM better remains incompletely understood.
基金Supported by the National Natural Science Foundation in China(No.81671641)Jiangsu Provincial Medical Innovation Team(No.CXTDA2017039)Gusu Health Talents Program(No.GSWS 2022018).
文摘AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.
文摘AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaertn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, SaMae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation.Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/reperfusion (I/R) in rats fed ethanol chronically.METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 rain of gut ischemia followed by 60 rain of reperfusion.Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 rain after the onset of superior mesenteric artery ocdusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion.Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia.RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats,the gut I/R-induced increases in the number of stationary leukooltes, plasma endotoxin levels and ALT activities were enhanced. Pretreat^nent with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption.CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.
文摘Background Cathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis,especially in the plaque destabilization and rupture leading to acute coronary syndrome.However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet. Methods Sprague-Dawley rats were randomly divided into three groups;Sham group,CME group and SB203580 group (n=10 per group).CME rats were produced by injection of 42μm microspheres into the left ventricle with occlusion of the ascending aorta.SB203580,a p38 MAPK inhibitor,was injected into femoral vein after finishing the injection of microspheres in SB203580 group.Left ventricular Ejection Fraction was determined by echocardiography.The level of phosphorylated and total P38 MAPK in myocardium was assessed by Western Blot.Results Left ventricular(LV) Ejection Fraction was depressed at 3 hours and until up to 12 hours in CME group.The increased p38 MAPK activation was observed in CME group.The administration of SB203580 partly inhibited the p38 MAPK activity and preserved cardiac contractile function.Conclusions p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly preserve cardiac contractile function.
基金supported by grants from the National Natural Science Foundation Project of China (NSFC) (No. 31571829 and No. 31640050)the People’s Livelihood Science and Technology Project Financially Supported by Qingdao city (No. 15-9-2-75-nsh)
文摘Propylene glycol alginate sodium sulfate-loaded nanoparticles(PSS-NP) has been shown potential to prevent the microvascular endothelial injuries caused by diabetic cardiomyopathy(DCM). In this study, we aimed to investigate the effects of PSS-NP on the dysfunction of cardiac microvascular endothelia in streptozotocin(STZ)-induced DCM rat model. Echocardiographic measurements showed a significant improvement of cardiac function in the PSS-NP-treated group. Our results revealed that the abnormalities of cardiac systolic and diastolic functions were suppressed by the treatments of prostaglandin E1(PGE1), low molecular weight heparin(LMWH), PSS and PSS-NP. Our comparison analysis indicated that PSS-NP showed the strongest inhibitory effects on microvascular endothelial injuries. Transmission electron microscopy analysis demonstrated that PSS-NP protected the cardiac microvascular endothelium and further improved endothelium dysfunction in DCM rats. ELISA and Western blot assays further showed a high efficiency of improving cardiac microvascular endothelial dysfunction with PSS-NP. Our results demonstrated that PSS-NP increased the protein expression of phosphatidylinositol 3-kinase(PI3K)-p85 and vascular endothelial growth factor(VEGF)-A, and the phosphorylation of protein kinase B(Akt) and endothelial nitric oxide synthase(eNOS), which were involved in the amelioration of cardiac microvascular endothelial dysfunction. These data suggest that PSS-NP may be a novel approach to the treatment the coronary microcirculation disorder diseases such as DCM.
文摘The incidence of both atrial fibrillation(AF)and coronary artery disease(CAD)increases with advancing age.They share common risk factors and very often coexist.Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level.In this review,we delineated this complex relationship,identified a common theme between the two,and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management.Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography.Further,the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship.CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity.AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system.In a nutshell,the two form a vicious cycle wherein one disease promotes the other.Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism.Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients.Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases.The relationship between AF and CAD is complex and much more than mere coincidence.The two diseases share common risk factor and pathophysiology.Hence,it is impractical to treat them in isolation.Accordingly,we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.
文摘Patients with ischemic cardiomyopathy constitute a heterogeneous group of patients with an extremely complex condition in which many factors play an important prognostic role. So it is difficult and probably unrealistic to expect that a single feature like presence of viable myocardium would provide an unequivocal answer to a critical question of revasculrization or not for all patients. Opposite to the hopes of investigators and physicians involved in the care of these patients, the findings of prospective studies with the use of different viability testing methods did not help in the decision-making process regarding CABG in ischemic cardiomyopathy. Instead, they left us with the same dilemma. The implication of most of these trials is that in patients with CAD and significant LV dysfunction, assessment of myocardial viability does not identify patients who will have the greatest survival benefit from adding CABG to aggressive medical therapy. In the clinical practice, these observations remind physicians to consider the multiplicity of factors involved in the decision-making process for patients with such a complex disease.
文摘Background: The intra-aortic balloon pumping (IABP) is the most used ventricular mechanical assist device. In recent years, the preoperative use in patients with severe ventricular dysfunction presents itself as a great benefic strategy to the postoperative recovery. This paper aim is to evaluate the IABP post-operative benefit in patients with severe ventricular dysfunction. Methods: From January 2011 to March 2016, 125 patients underwent a coronary artery bypass graft (CABG) with cardiopulmonary bypass and preoperative IABP in Teaching Hospital of the ABC Medical School and Hospital Estadual Mario Covas. The inclusion criteria were the presence of severe ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) less than or equal to 40%, estimated by Doppler echocardiography using the Simpson method. The preoperative LVEF was 30.25% ± 8.53% and the diastolic diameter of the left ventricle (LVDD) 67.75 ± 16.37 mm. IABP was installed approximately 15 hours before the surgery. Results: The patients required the IABP for 2.4 ± 1.58 days, and vasoactive drugs, 4.8 ± 2.12 days. We performed 3.2 ± 1.9 grafts per patient and the total length of stay was 07 ± 5.52 days. Cardiopulmonary bypass time was 67 ± 10.95 minutes and anoxia time, 46.4 ± 10.06 minutes. Twelve patients (9.6%) had pneumonia and four (3.2%), atrial fibrillation. We observed a LVDD reduction to 63 ± 16.26 (p = 0.068) and LVEF enhancement to 36.50 ± 16.86 (p = 0.144). The data were analyzed statistically according to the Wilcoxon test. There were no deaths. Conclusion: The initial experience of the authors with the preoperative IABP in patients with severe left ventricular dysfunction suggests great benefit in post-operative recovery with im-provement of LVEF and reduction of LVDD.
文摘Objectives To evaluate the relationship of renal dysfunction,coronary heart disease and percutaneous coronary intervention(PCI).Methods(l)The subjects:There were 376 patients who come from department of cardiology of our hospital in this study undergoing coronary angiography.The patients were divided into two groups? according to coronary angiography:coronary artery disease(group A,n =263),in which 141 patients with renal dysfunction(group A1) and 122 patients with normal renal function(group A2):patients with other kinds of cardiovascular disease but normal coronary angiography(group B.n=113).Before the coronary angiography, all patients were measured the serum creatinine, microalbuminuria,fasting blood-glucose,triglycerides,total cholesterol,high density lipoprotein,low density lipoprotein, blood pressure in fasting 12 hours.(2)The diagnostic criteria for renal dysfunction:male serum creatinine】115 umol/L and/or microalbuminuria】30 mg,female】107 umol/L and/ or】30 mg.Results(1)The differences of renal function indexes in the group A and B:The mean level of microalbuminuria and serum creatinine was higher significantly in group A than that of the group B(43.48±38.93 vs.11.23±7.07 and 101.52±37.22 vs.80.62±17.4 respectively.Conclusions The coronary heart disease patients with renal dysfunction had more severe coronary artery stenosis,The renal dysfunction is a strong and independent risk factors for the coronary heart disease and beeds more revascularization therapy.
