Percutaneous coronary intervention(PCI),as an essential treatment for coronary artery disease,has significantly improved the prognosis of patients with large coronary artery lesions.However,some patients continue to e...Percutaneous coronary intervention(PCI),as an essential treatment for coronary artery disease,has significantly improved the prognosis of patients with large coronary artery lesions.However,some patients continue to experience myocar-dial ischemic symptoms post-procedure,largely due to coronary microvascular dysfunction(CMD).The pathophysiological mechanisms of CMD are complex and involve endothelial dysfunction,microvascular remodeling,reperfusion in-jury,and metabolic abnormalities.Moreover,components of metabolic syndrome,including obesity,hyperglycemia,hypertension,and dyslipidemia,exacerbate the occurrence and progression of CMD through multiple pathways.This review systematically summarizes the latest research advan-cements in CMD after PCI,including its pathogenesis,diagnostic techniques,management strategies,and future research directions.For diagnosis,invasive techniques such as coronary flow reserve and the index of microcirculatory resistance,as well as non-invasive imaging modalities(positron emission tomography and cardiac magnetic reso-nance),provide tools for early CMD detection.In terms of management,a multi-level intervention strategy is emphasized,incorporating lifestyle modifications(diet,exercise,and weight control),pharmacotherapy(vasodilators,hypoglycemic agents,statins,and metabolic modulators),traditional Chinese medicine,and specialized treatments(enhanced external counterpulsation,metabolic surgery,and lipoprotein apheresis).However,challenges remain in CMD treatment,including limitations in diagnostic tools and the lack of personalized treatment strategies.Future research should focus on the complex interactions between CMD and metabolic risks,aiming to optimize diagnostic and therapeutic strate-gies to improve the long-term prognosis of patients post-PCI.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
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
To the Editor:More than half of the patients undergoing invasive coronary angiography for angina or signs of myocardial ischemia present with non-obstructive coronary arteries(NOCA,<50%diameter reduction or fractio...To the Editor:More than half of the patients undergoing invasive coronary angiography for angina or signs of myocardial ischemia present with non-obstructive coronary arteries(NOCA,<50%diameter reduction or fractional flow reserve>0.80).[1]Coronary microvascular dysfunction(CMD)is a significant pathophysiological factor in these patients and is linked to adverse outcomes.[2]Although coronary reactivity testing(CRT)remains the gold standard for diagnosing CMD,it is both invasive and costly.Stress cardiac magnetic resonance(CMR)is a non-invasive and promising alternative,providing essential perfusion parameters such as myocardial perfusion reserve index(MPRI)and myocardial perfusion reserve(MPR)to diagnose CMD.Thus,based on current literature,there is robust evidence supporting the effectiveness of stress CMR in diagnosing CMD in patients with NOCA,as defined by CRT.展开更多
Coronary microvascular dysfunction(CMD)is a clinical syndrome of myocardial ischemia caused by structural and/or functional abnormalities of pre-coronary arterioles and arterioles.While genetics and other factors play...Coronary microvascular dysfunction(CMD)is a clinical syndrome of myocardial ischemia caused by structural and/or functional abnormalities of pre-coronary arterioles and arterioles.While genetics and other factors play a role in CMD etiology,the key pathogenic mechanism remains unclear.Currently,the diagnostic procedure for CMD is still cumbersome,and there is a lack of effective targeted interventions.Single nucleotide polymorphisms(SNPs)offer promise in addressing these issues.SNPs,reflecting common genetic variations,have garnered extensive investigation across multiple diseases.Several sNPs associated with CMD have been discovered,and some have the potential to be therapeutic targets.Nevertheless,studies on CMD-related SNPs are relatively nascent and limited in number.In this review,we summarize the previously reported CMD-associated SNPs,delineate their pathophysiological mechanisms,and predict potentially important CMD sites by analyzing the SNPs linked to diseases sharing similar pathogenetic mechanisms and risk factors,such as coronary artery disease.We aim to explore reliable genetic markers implicated in CMD risk and prognosis,thereby providing a novel approach for early diagnosis and gene-targeted interventions of CMD in subsequent studies.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
Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease.Its pathophysiology involves atheroscle...Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease.Its pathophysiology involves atherosclerotic and nonatherosclerotic mechanisms such as plaque erosion,coronary microvascular dysfunction,vasospasm,spontaneous coronary artery dissection,autoimmune and inflammatory diseases,and myocardial oxygen supply-demand imbalance.A systematic approach to diagnosis is needed due to the diverse range of underlying causes.Cardiac troponins confirm the myocardial injury and coronary angiography rules out significant obstruction.Cardiac magnetic resonance imaging differentiates ischemic from nonischemic causes,and additional investigations,such as intravascular ultrasound,optical coherence tomography,and provocative testing,play a role in identifying the etiology to guide management strategies.Atherosclerotic cases require antiplatelet therapy and statins,vasospastic cases respond to calcium channel blockers,spontaneous coronary artery dissection is typically managed conservatively,and coronary microvascular dysfunction may require vasodilators.Lifestyle modifications and cardiac rehabilitation are essential for improving outcomes.The prognosis of patients experiencing recurrent events despite treatment is uncertain,but long-term outcomes depend on the etiology,highlighting the need for personalized management.Future research should focus on refining diagnostic protocols and identifying optimal therapeutic strategies.Randomized controlled trials are necessary to establish evidence-based treatments for different subtypes of myocardial infarction with nonobstructive coronary arteries.展开更多
Objective To evaluate the prevalence,potential risk factors,and correlation between coronary and peripheral microvascular dysfunction in heart failure with nonreduced ejection fraction(nHFrEF)patients.Methods This was...Objective To evaluate the prevalence,potential risk factors,and correlation between coronary and peripheral microvascular dysfunction in heart failure with nonreduced ejection fraction(nHFrEF)patients.Methods This was a prospective registry study.nHFrEF patients admitted to Zhongshan Hospital affiliated with Fudan University from December 2021 to December 2023 were enrolled.According to coronary flow reserve(CFR)or reactive congestion index(RHI),enrolled patients were divided into coronary microvascular endothelial dysfunction(CMD)group(CFR<2.5)and no CMD group(CFR≥2.5)or peripheral microvascular endothelial dysfunction(MED)group(RHI<1.67)and no MED group(RHI≥1.67).Patients'general information,laboratory and auxiliary examination data were collected.Univariate and multivariate logistic regression were used to analyze the influencing factors of CMD and MED in nHFrEF patients,and Spearman correlation analysis was used to evaluate the correlation between MED and CMD.Results A total of 142 nHFrEF patients were enrolled,aged 69.0(59.0,74.0)years,with a male proportion of 66.9%(95/142).The grouping results were as follows:(1)According to CFR,there were 73 cases in the CMD group and 69 cases in the no CMD group;(2)According to RHI,there were 57 cases in the MED group and 85 cases in the no MED group.The prevalence of CMD and MED in this study was 51.4%(73/142)and 40.1%(57/142),respectively.Univariate logistic regression analysis showed that increased heart rate,chronic kidney disease,atrial fibrillation,elevated N-terminal pro-B type natriuretic peptide levels,and increased urinary albumin/creatinine ratio were risk factors for CMD,while increased RHI was a protective factor for CMD;Atrial fibrillation is a risk factor for MED,while increased CFR isa protectivefactor for MED.Incorporating clinically significant variables from univariate analysis into multivariate analysis,the results showed that increased heart rate and elevated RHI remained risk and protective factors for CMD,respectively;increased CFR remains a protective factor for MED.Spearman correlation analysis showed that CFR was negatively correlated with lg urinary albumin/creatinine ratio,lg cardiac troponin T,lg N-terminal pro-B type natriuretic peptide,and heart rate;RHI is positively correlated with CFR.Conclusion The prevalence of CMD and MED in nHFrEF patients is high,and the two have a certain positive correlation.Increased heart rate and RHI are risk and protective factors for CMD,respectively,while increased CFR is a protective factor for MED.MED may be a potential therapeutic target for nHFrEF patients.展开更多
OBJECTIVE:To investigate the protective effect of matrine on coronary microvascular dysfunction(CMD)induced by advanced glycation end products(AGEs)in a mouse model of ischemia with non-obstructive coronary artery dis...OBJECTIVE:To investigate the protective effect of matrine on coronary microvascular dysfunction(CMD)induced by advanced glycation end products(AGEs)in a mouse model of ischemia with non-obstructive coronary artery disease(INOCA),with a focus on the underlying mechanisms,particularly the endoplasmic reticulum(ER)stress protein kinase R-like ER kinase(PERK)/nuclear factor of activated T-cells(NFAT)signaling pathway.METHODS:An INOCA model was established in mice,and CMD was induced by peritoneal injections of AGEs.Matrine was administered daily via intraperitoneal injections.Coronary microcirculation was evaluated using coronary flow velocity reserve(CFVR),and cardiac microvascular endothelial cells(CMECs)were isolated for assessment of apoptosis,inflammation,oxidative stress,and microthrombosis.Markers of ER stress and the PERK/NFAT pathway were examined through immunoblotting,immunofluorescence,and enzymatic assays.The effect of matrine were further evaluated in CMECs treated with AGEs and the PERK agonist.RESULTS:Matrine treatment significantly improved CFVR and reduced CMD in AGEs-exposed INOCA mice.In CMECs,matrine attenuated AGEs-induced apoptosis,inflammation,and microthrombosis.It also suppressed intracellular reactive oxygen species(ROS)generation,ER stress markers,and PERK/NFAT signaling.Matrine's effects were concentration-dependent and partially reversed by the PERK agonist,confirming its action through the ER stress pathway.No significant toxicities were observed with matrine administration.CONCLUSION:Matrine attenuates AGEs-induced CMD in INOCA by suppressing the ROS-mediated ER stress PERK/NFAT signaling pathway in CMECs.This study highlights matrine's potential as a therapeutic agent for CMD in diabetic cardiovascular complications.展开更多
Stress-induced cardiomyopathy,in contrast to acute myocardial infarction,is a type of acute heart failure characterized by reversible left ventricular dysfunction.Cardiac imaging primarily reveals left ventricle myoca...Stress-induced cardiomyopathy,in contrast to acute myocardial infarction,is a type of acute heart failure characterized by reversible left ventricular dysfunction.Cardiac imaging primarily reveals left ventricle myocardial stunning,81.7%of which is apical type.Emotional or psychological stress usually precedes the onset of stress-induced cardiomyopathy,which is increasingly being recognized as a unique neurogenic myocardial stunning disease.To distinguish between acute myocardial infarction and acute viral or auto-immune myocarditis,this review summarizes specific mechanisms of myocardial stunning in stress-induced cardiomyopathy,such as calcium disorders,metabolic alterations,anatomical and histological variations in different parts of the left ventricle,and microvascular dysfunction.展开更多
CD34+cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine.Naturally,these cells are mobilized from the bone marrow into peripheral circulati...CD34+cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine.Naturally,these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury.CD34+cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage.They have an important paracrine activity in secreting factors to stimulate vasculogenesis,reduce endothelial cells and cardiomyocytes apoptosis,remodel extracellular matrix and activate additional progenitor cells.Once they migrate to the target site,they enhance angiogenesis,neovascularization and tissue regeneration.Several trials have demonstrated the safety and efficacy of CD34+cell therapy in different settings,such as peripheral limb ischemia,stroke and cardiovascular disease.Herein,we review the potential utility of CD34+cell transplantation in acute myocardial infarction,refractory angina and ischemic heart failure.展开更多
Vasospastic angina(VSA)is a distinct endotype of ischemia with non-obstructive coronary arteries characterized by transient coronary artery spasm and myocardial ischemia in the absence of significant fixed stenosis.It...Vasospastic angina(VSA)is a distinct endotype of ischemia with non-obstructive coronary arteries characterized by transient coronary artery spasm and myocardial ischemia in the absence of significant fixed stenosis.It is an underdiagnosed and often challenging condition that can lead to recurrent angina,myocardial infarction,and sudden cardiac death.VSA arises from a multifactorial interplay of endothelial dysfunction,vascular smooth muscle hyperreactivity,inflammation,and autonomic dysregulation.While calcium channel blockers and nitrates remain the mainstay of therapy,there is a growing body of evidence in the use of novel and emerging treatments including Rho-kinase inhibitors,endothelin receptor antagonists,and anti-inflammatory agents for refractory cases.Diagnostic evaluation relies on clinical features and,when necessary,invasive coronary pharmacological provocation testing.This narrative review examines the current understanding of VSA,discusses current international guideline-based diagnostic and therapeutic strategies,and highlights novel and investigational approaches that may broaden the treatment armamentarium against it.展开更多
文摘Percutaneous coronary intervention(PCI),as an essential treatment for coronary artery disease,has significantly improved the prognosis of patients with large coronary artery lesions.However,some patients continue to experience myocar-dial ischemic symptoms post-procedure,largely due to coronary microvascular dysfunction(CMD).The pathophysiological mechanisms of CMD are complex and involve endothelial dysfunction,microvascular remodeling,reperfusion in-jury,and metabolic abnormalities.Moreover,components of metabolic syndrome,including obesity,hyperglycemia,hypertension,and dyslipidemia,exacerbate the occurrence and progression of CMD through multiple pathways.This review systematically summarizes the latest research advan-cements in CMD after PCI,including its pathogenesis,diagnostic techniques,management strategies,and future research directions.For diagnosis,invasive techniques such as coronary flow reserve and the index of microcirculatory resistance,as well as non-invasive imaging modalities(positron emission tomography and cardiac magnetic reso-nance),provide tools for early CMD detection.In terms of management,a multi-level intervention strategy is emphasized,incorporating lifestyle modifications(diet,exercise,and weight control),pharmacotherapy(vasodilators,hypoglycemic agents,statins,and metabolic modulators),traditional Chinese medicine,and specialized treatments(enhanced external counterpulsation,metabolic surgery,and lipoprotein apheresis).However,challenges remain in CMD treatment,including limitations in diagnostic tools and the lack of personalized treatment strategies.Future research should focus on the complex interactions between CMD and metabolic risks,aiming to optimize diagnostic and therapeutic strate-gies to improve the long-term prognosis of patients post-PCI.
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 the National Key R&D Program of China(Nos.2021YFF0501400 and 2021YFF0501404)the Key Project of National Natural Science Foundation of China(No.81930044).
文摘To the Editor:More than half of the patients undergoing invasive coronary angiography for angina or signs of myocardial ischemia present with non-obstructive coronary arteries(NOCA,<50%diameter reduction or fractional flow reserve>0.80).[1]Coronary microvascular dysfunction(CMD)is a significant pathophysiological factor in these patients and is linked to adverse outcomes.[2]Although coronary reactivity testing(CRT)remains the gold standard for diagnosing CMD,it is both invasive and costly.Stress cardiac magnetic resonance(CMR)is a non-invasive and promising alternative,providing essential perfusion parameters such as myocardial perfusion reserve index(MPRI)and myocardial perfusion reserve(MPR)to diagnose CMD.Thus,based on current literature,there is robust evidence supporting the effectiveness of stress CMR in diagnosing CMD in patients with NOCA,as defined by CRT.
基金supported by the Chongqing Key Project of Science and Technology Joint Medical Research (China) (No.2019ZDXM013 to Z.H.Z.)the Chongqing Talent Program (China) (No.CQYC20210303360 to Z.H.Z.).
文摘Coronary microvascular dysfunction(CMD)is a clinical syndrome of myocardial ischemia caused by structural and/or functional abnormalities of pre-coronary arterioles and arterioles.While genetics and other factors play a role in CMD etiology,the key pathogenic mechanism remains unclear.Currently,the diagnostic procedure for CMD is still cumbersome,and there is a lack of effective targeted interventions.Single nucleotide polymorphisms(SNPs)offer promise in addressing these issues.SNPs,reflecting common genetic variations,have garnered extensive investigation across multiple diseases.Several sNPs associated with CMD have been discovered,and some have the potential to be therapeutic targets.Nevertheless,studies on CMD-related SNPs are relatively nascent and limited in number.In this review,we summarize the previously reported CMD-associated SNPs,delineate their pathophysiological mechanisms,and predict potentially important CMD sites by analyzing the SNPs linked to diseases sharing similar pathogenetic mechanisms and risk factors,such as coronary artery disease.We aim to explore reliable genetic markers implicated in CMD risk and prognosis,thereby providing a novel approach for early diagnosis and gene-targeted interventions of CMD in subsequent studies.
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Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease.Its pathophysiology involves atherosclerotic and nonatherosclerotic mechanisms such as plaque erosion,coronary microvascular dysfunction,vasospasm,spontaneous coronary artery dissection,autoimmune and inflammatory diseases,and myocardial oxygen supply-demand imbalance.A systematic approach to diagnosis is needed due to the diverse range of underlying causes.Cardiac troponins confirm the myocardial injury and coronary angiography rules out significant obstruction.Cardiac magnetic resonance imaging differentiates ischemic from nonischemic causes,and additional investigations,such as intravascular ultrasound,optical coherence tomography,and provocative testing,play a role in identifying the etiology to guide management strategies.Atherosclerotic cases require antiplatelet therapy and statins,vasospastic cases respond to calcium channel blockers,spontaneous coronary artery dissection is typically managed conservatively,and coronary microvascular dysfunction may require vasodilators.Lifestyle modifications and cardiac rehabilitation are essential for improving outcomes.The prognosis of patients experiencing recurrent events despite treatment is uncertain,but long-term outcomes depend on the etiology,highlighting the need for personalized management.Future research should focus on refining diagnostic protocols and identifying optimal therapeutic strategies.Randomized controlled trials are necessary to establish evidence-based treatments for different subtypes of myocardial infarction with nonobstructive coronary arteries.
文摘Objective To evaluate the prevalence,potential risk factors,and correlation between coronary and peripheral microvascular dysfunction in heart failure with nonreduced ejection fraction(nHFrEF)patients.Methods This was a prospective registry study.nHFrEF patients admitted to Zhongshan Hospital affiliated with Fudan University from December 2021 to December 2023 were enrolled.According to coronary flow reserve(CFR)or reactive congestion index(RHI),enrolled patients were divided into coronary microvascular endothelial dysfunction(CMD)group(CFR<2.5)and no CMD group(CFR≥2.5)or peripheral microvascular endothelial dysfunction(MED)group(RHI<1.67)and no MED group(RHI≥1.67).Patients'general information,laboratory and auxiliary examination data were collected.Univariate and multivariate logistic regression were used to analyze the influencing factors of CMD and MED in nHFrEF patients,and Spearman correlation analysis was used to evaluate the correlation between MED and CMD.Results A total of 142 nHFrEF patients were enrolled,aged 69.0(59.0,74.0)years,with a male proportion of 66.9%(95/142).The grouping results were as follows:(1)According to CFR,there were 73 cases in the CMD group and 69 cases in the no CMD group;(2)According to RHI,there were 57 cases in the MED group and 85 cases in the no MED group.The prevalence of CMD and MED in this study was 51.4%(73/142)and 40.1%(57/142),respectively.Univariate logistic regression analysis showed that increased heart rate,chronic kidney disease,atrial fibrillation,elevated N-terminal pro-B type natriuretic peptide levels,and increased urinary albumin/creatinine ratio were risk factors for CMD,while increased RHI was a protective factor for CMD;Atrial fibrillation is a risk factor for MED,while increased CFR isa protectivefactor for MED.Incorporating clinically significant variables from univariate analysis into multivariate analysis,the results showed that increased heart rate and elevated RHI remained risk and protective factors for CMD,respectively;increased CFR remains a protective factor for MED.Spearman correlation analysis showed that CFR was negatively correlated with lg urinary albumin/creatinine ratio,lg cardiac troponin T,lg N-terminal pro-B type natriuretic peptide,and heart rate;RHI is positively correlated with CFR.Conclusion The prevalence of CMD and MED in nHFrEF patients is high,and the two have a certain positive correlation.Increased heart rate and RHI are risk and protective factors for CMD,respectively,while increased CFR is a protective factor for MED.MED may be a potential therapeutic target for nHFrEF patients.
基金National Natural Scientific Foundation of China:Mechanisms of Macrophage-Mediated Vascular Smooth Muscle Cells Phenotypic Conversion in Advanced Glycation End Products-induced Atherosclerosis and Therapeutic Effects of Targeted Gene Silencing(82070858)Youth Scientific Research and Innovation Team Program of Shaanxi Province:Diabetes-Related Atherosclerosis Basic Research and Application Research Team(2022-SLRH-LJ-014)。
文摘OBJECTIVE:To investigate the protective effect of matrine on coronary microvascular dysfunction(CMD)induced by advanced glycation end products(AGEs)in a mouse model of ischemia with non-obstructive coronary artery disease(INOCA),with a focus on the underlying mechanisms,particularly the endoplasmic reticulum(ER)stress protein kinase R-like ER kinase(PERK)/nuclear factor of activated T-cells(NFAT)signaling pathway.METHODS:An INOCA model was established in mice,and CMD was induced by peritoneal injections of AGEs.Matrine was administered daily via intraperitoneal injections.Coronary microcirculation was evaluated using coronary flow velocity reserve(CFVR),and cardiac microvascular endothelial cells(CMECs)were isolated for assessment of apoptosis,inflammation,oxidative stress,and microthrombosis.Markers of ER stress and the PERK/NFAT pathway were examined through immunoblotting,immunofluorescence,and enzymatic assays.The effect of matrine were further evaluated in CMECs treated with AGEs and the PERK agonist.RESULTS:Matrine treatment significantly improved CFVR and reduced CMD in AGEs-exposed INOCA mice.In CMECs,matrine attenuated AGEs-induced apoptosis,inflammation,and microthrombosis.It also suppressed intracellular reactive oxygen species(ROS)generation,ER stress markers,and PERK/NFAT signaling.Matrine's effects were concentration-dependent and partially reversed by the PERK agonist,confirming its action through the ER stress pathway.No significant toxicities were observed with matrine administration.CONCLUSION:Matrine attenuates AGEs-induced CMD in INOCA by suppressing the ROS-mediated ER stress PERK/NFAT signaling pathway in CMECs.This study highlights matrine's potential as a therapeutic agent for CMD in diabetic cardiovascular complications.
基金supported primarily by the Distinguished Young Foundations of the First Affiliated Hospital of Harbin Medical University(HYD2020JQ002 to Dr Yin)The Science Foundation of the First Affiliated Hospital of Harbin Medical University(2018 L001 to Dr Yin).
文摘Stress-induced cardiomyopathy,in contrast to acute myocardial infarction,is a type of acute heart failure characterized by reversible left ventricular dysfunction.Cardiac imaging primarily reveals left ventricle myocardial stunning,81.7%of which is apical type.Emotional or psychological stress usually precedes the onset of stress-induced cardiomyopathy,which is increasingly being recognized as a unique neurogenic myocardial stunning disease.To distinguish between acute myocardial infarction and acute viral or auto-immune myocarditis,this review summarizes specific mechanisms of myocardial stunning in stress-induced cardiomyopathy,such as calcium disorders,metabolic alterations,anatomical and histological variations in different parts of the left ventricle,and microvascular dysfunction.
文摘CD34+cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine.Naturally,these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury.CD34+cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage.They have an important paracrine activity in secreting factors to stimulate vasculogenesis,reduce endothelial cells and cardiomyocytes apoptosis,remodel extracellular matrix and activate additional progenitor cells.Once they migrate to the target site,they enhance angiogenesis,neovascularization and tissue regeneration.Several trials have demonstrated the safety and efficacy of CD34+cell therapy in different settings,such as peripheral limb ischemia,stroke and cardiovascular disease.Herein,we review the potential utility of CD34+cell transplantation in acute myocardial infarction,refractory angina and ischemic heart failure.
文摘Vasospastic angina(VSA)is a distinct endotype of ischemia with non-obstructive coronary arteries characterized by transient coronary artery spasm and myocardial ischemia in the absence of significant fixed stenosis.It is an underdiagnosed and often challenging condition that can lead to recurrent angina,myocardial infarction,and sudden cardiac death.VSA arises from a multifactorial interplay of endothelial dysfunction,vascular smooth muscle hyperreactivity,inflammation,and autonomic dysregulation.While calcium channel blockers and nitrates remain the mainstay of therapy,there is a growing body of evidence in the use of novel and emerging treatments including Rho-kinase inhibitors,endothelin receptor antagonists,and anti-inflammatory agents for refractory cases.Diagnostic evaluation relies on clinical features and,when necessary,invasive coronary pharmacological provocation testing.This narrative review examines the current understanding of VSA,discusses current international guideline-based diagnostic and therapeutic strategies,and highlights novel and investigational approaches that may broaden the treatment armamentarium against it.
