脑梗死患者ACE活性及基因多态性的变化

血管紧张素转换酶 (ACE)又称激肽酶 ,在血管紧张素 的产生和缓激肽的分解代谢中起着关键性的作用 ,ACE是肾素 -血管紧张素系统 (RAS)中的限速酶 ,参与维持血管结构、血管重构和动脉粥样硬化的形成。目前已发现 ACE基因呈多态性 ,被认为是研究高血压及心脑血管疾病的主要候选基     

血管紧张素转换酶2与心血管系统

血管紧张素转换酶2(ACE2)是2000年由国外学者发现的一个新的锌脂金属蛋白酶,对肾素-血管紧张素系统(RAS)具有关键性调控作用。主要由心脏、肾脏、睾丸的血管内皮细胞表达。因其内含有一个HEXXH锌结合体motif,并在这一结合体附近与血管紧张素转换酶(ACE)高度同源[1],故称ACE2或血管转换酶同源体(ACEH)。能水解血管紧张素Ⅰ(AngⅠ),产生AngⅠ-9,水解血管紧张素Ⅱ(AngⅡ),产生AngⅠ-7[2]。ACE2在RAS中的作用与ACE相反,保持血管的收缩与舒张平衡,与高血压、心力衰竭(心衰)及冠心病等相关。1 ACE2的生物学特性1.1 ACE2的结构及功…     

血管紧张素转换酶2对动脉粥样硬化的作用研究现状

<正>肾素-血管紧张素(Ang)-醛固酮系统(RAS)在心血管疾病的发生、发展中起重要作用。近年来随着人们对RAS的不断深入研究发现,由血管紧张素转换酶(ACE)2参与的ACE2-Ang-(1～7)-G蛋白耦联(MAS)轴,具有舒张血管、抑制心血管重构等作用。ACE2的基因多态性也和动脉粥样硬化(AS)存在相关性。本文对ACE2与AS的相关性研究进展进行综述。1 AngⅡ导致AS的机制RAS作为心血管系统功能的主要调节因子,对AS的发     

缺血性或原发性扩张型心肌病患者ACEDD基因型的临床意义

肾素-血管紧张素系统通过血管紧张素Ⅱ调节血压参与心血管疾患的发病过程。血管紧张素Ⅱ是一种有效的血管收缩剂,并能刺激血管平滑肌细胞的增生,在动脉损害后粥样硬化的形成起重要作用,且可通过对心肌细胞营养的影响,导致急性心梗后心脏的异常重构。为探讨ACE基因分子变异的作用,作者对缺血性心肌病(ISC)患者、扩张     

血管紧张素转换酶基因多态性与慢性阻塞性肺病

本文介绍了血管紧张素转换酶(ACE)的生物学特性，遗传学特性及ACE基因多态性及其基因多态性与慢性阻塞性肺病的气道重构，肺血管重构的关联。     

慢性心力衰竭患者血管紧张素转换酶及血管紧张素转换酶2表达的变化

血管紧张素转换酶(ACE)的酶解产物是血管紧张素Ⅱ(Ang II),过量的Ang II能导致心肌细胞肥大、坏死、凋亡,心肌间质纤维化,诱发心肌重构.ACE2是2000年才发现的ACE的同系物,主要生物学效应是降解AngⅡ,生成Angl-7.由此看来,ACE和ACE2是一对功能效应相反的酶.我们设想,ACE和ACE2的表达失衡参与了慢性心力衰竭(CHF)的发病过程.     

血管紧张素-(1-9)心脏保护性作用研究进展

2000年,由血管紧张素转换酶(ACE)2、血管紧张素(Ang)-(1-9)和Ang-(1-7)以及Mas受体组成的新型肾素—血管紧张素—醛固酮系统(RAAS)被发现。目前已证实ACE2/Ang-(1-7)/Mas受体轴的生理学作用与ACE/AngⅡ/血管紧张素1型受体(AT1R)轴是相拮抗的。近来数据显示Ang-(1-9)可以保护高血压伴或不伴心力衰竭的患者使其心脏重构减弱。可能为RAAS的完整性描述提供新的依据。     

ACE基因多态性与原发性高血压患者血清ACE及AngⅡ浓度的关系

目的　研究原发性高血压患者血管紧张素转换酶 (ACE)基因多态性与血清血管紧张素转换酶及血管紧张素Ⅱ浓度的关系。方法　应用聚合酶链反应技术 (PCR)检测 82 1例高血压患者的ACE基因型 ,同时测定其血清ACE水平、血管紧张素Ⅱ浓度及醛固酮浓度 ,比较不同基因型患者其血清ACE、血管紧张素Ⅱ和醛固酮水平有无差别。结果　II、ID、DD基因型患者血清ACE水平分别为 ( 3 2 0 9± 15 62 )U/L ,( 4 1 46± 16 67)U/L和 ( 4 7 60± 19 5 4)U/L ;组间差异具有显著性(P <0 0 1) ;三组基因型患者血管紧张素Ⅱ水平分别为 ( 63 78± 2 9 86) pg/mL ,( 63 89± 2 9 19) pg/mL和 ( 62 3 5± 2 0 66)pg/mL ,三者差别无统计学意义 ;醛固酮浓度在三种基因型患者中分别是 ( 15 1 98± 5 2 91)ng/L ,( 15 5 3 9± 49 91)ng/L和( 171 82± 43 82 )ng/L ,组间差异具有显著性 (P <0 0 1)。多元线性回归结果表明DD基因型是影响血清ACE水平的主要因素 ,但对血管紧张素Ⅱ水平无影响。结论　不同ACE基因型患者血清ACE水平存在明显差异 ,DD基因型患者血清ACE水平明显高于ID型和II型患者。血管紧张素Ⅱ水平在三种基因型间无明显差异     

血管紧张素转换酶2/apelin信号与高血压靶器官损害

该文阐述了血管紧张素转换酶(angiotensin converting enzyme,ACE)2/apelin信号在高血压及其靶器官损害发生、发展中的重要调控作用,以及对肾素血管紧张素醛固酮系统(renin-angiotensin-aldosterone system,RAAS)异常激活所具有的负性调控作用,并认为ACE与ACE2的比值很可能是血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitor,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blocker,ARB)降压作用的新机制。ACE2/apelin信号为未来研发心血管保护药物提供了新的方向。     

血管紧张素转换酶2研究新进展

血管紧张素转换酶(ACE)是一种锌指金属蛋白酶,对肾素-血管紧张素系统(RAS)有关键调控作用.ACE 2主要分布在心脏、肾脏和睾丸,能水解血管紧张素(Ang)Ⅰ,产生Ang 1-9,还能水解RAS中的主要物质AngⅡ,产生具有血管扩张作用的Ang 1-7.研究表明ACE 2可能在RAS中扮演与ACE相反的角色,达到血管收缩和舒张之间的平衡,与高血压、心力衰竭及糖尿病肾病等关系密切.     

Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice

OBJECTIVES: The peptidase action of angiotensin converting enzyme 2 (ACE2) allows it to function as a negative regulator of the renin-angiotensin system. Current pharmacotherapies for human heart failure, such as ACE inhibitors and angiotensin and aldosterone receptor blockers, increase the activity of ACE2 in the heart. In this study, we investigate the mechanism for the age-dependent cardiomyopathy in ACE2 null mice. METHODS AND RESULTS: Ace2(-/y) mutant mice develop a progressive age-dependent dilated cardiomyopathy with increased oxidative stress, neutrophilic infiltration, inflammatory cytokine and collagenase levels, mitogen-activated protein kinase (MAPK) activation and pathological hypertrophy. The angiotensin II receptor-1 (AT1) blocker, irbesartan, prevented the dilated cardiomyopathy in aged Ace2(-/y) mutant mice, confirming a critical role of angiotensin II (Ang II)-mediated stimulation of AT1 receptors. Ang II activation of AT1 receptors triggers G-protein-coupled receptor (GPCR)-activated phosphoinositide 3-kinase gamma (PI3Kgamma) and its downstream pathways. We showed that p110gamma, the catalytic subunit of PI3Kgamma, is a key mediator of NADPH oxidase activation in response to Ang II. The double mutant mice (Ace2(-/y)/p110gamma(-/-)) exhibited marked reductions in oxidative stress, neutrophilic infiltration, and pathological hypertrophy resulting in myocardial protection, suggesting that PI3Kgamma plays a critical role in Ang II-mediated cardiomyopathy. CONCLUSIONS: Our findings demonstrate that the age-dependent cardiomyopathy in ACE2 null mice is related to increased Ang II-mediated oxidative stress and neutrophilic infiltration via AT1 receptors. Our combination of genetic and pharmacological approaches defines a critical role of ACE2 in the suppression of Ang II-mediated heart failure.     

The role of angiotensin-converting enzyme polymorphism in congestive heart failure

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase, with primary known functions of converting angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and inactivating bradykinin. There is high variability among individuals in ACE concentrations, mainly due to the presence of a genetic polymorphism. The ACE gene has, in fact, insertion/deletion polymorphism in intron 16, consisting of a 287-base pair Alu repeat sequence, with three genotypes: insertion polymorphism, insertion/deletion polymorphism, and deletion polymorphism. The genetic effect accounts for 47% of the total variance of serum ACE. The determination of this polymorphism has allowed researchers to study the implications of the ACE gene in many case-control studies of cardiovascular disease, including myocardial infarction and hypertrophic and dilated cardiomyopathy. We review the current knowledge about the ACE gene polymorphism and its implications in heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Interpretation of the results of studies about the role of this polymorphism are controversial. The repetition of epidemio-genetic studies and the creation of adequate experimental studies will help to definitively establish the pathogenetic role of the permanent increase in ACE expression associated with the deletion polymorphism genotype.     

Treatment of cardiac insufficiency: does treatment depend on whether its cause is ischemic or idiopathic?]

Angiotensin converting enzyme (ACE) inhibitors are associated with a greater reduction in mortality in non-ischaemic cardiomyopathy than in ischaemic cardiomyopathy after the results of the V-HeFT-II and SOLVD trials in symptomatic patients. However, a recent analysis of the global, symptomatic and therapeutic, results of the SOLVD trials, demonstrated a similar reduction in mortality with ACE inhibitors in ischaemic and non-ischaemic cardiomyopathies. Moreover, after myocardial infarction, the beneficial effects of ACE inhibitors have been well established in patients with left ventricular dysfunction. Betablockers, especially bisoprolol in the CIBIS-I trial, also seem to be more effective in non-ischaemic cardiomyopathy. However, CIBIS-II and the US Carvedilol Heart Failure Trial Program clearly showed that the benefits of betablockade were identical whether ischaemic or not. The beneficial effects of betablockers in the post-infarction period are more marked when left ventricular dysfunction is severe. The PROVED and RADIANCE trials suggest that digitalis is more effective in non-ischaemic cardiomyopathy. These results were not confirmed by the DIG trial which showed a significant reduction in the combined criterion, mortality and hospital admission for aggravation of cardiac failure, both in ischaemic and in non-ischaemic cardiomyopathy. However, the use of digitalis should be prudent during ischaemic cardiomyopathy, the neutral effect on global mortality in the DIG trial masking divergent results with a tendency to reducing mortality due to aggravation of cardiac failure and a significant increase of other causes of cardiac death, especially from myocardial infarction and arrhythmias. Amiodarone could also be useful in non-ischaemic cardiomyopathy. The reduction in risk of death in the GESICA study, which comprised 60% of patients with non-ischaemic cardiomyopathy, contrasting with the absence of an effect with this molecule in the STAT-CHF trial which only comprised 29% of patients with non-ischaemic cardiomyopathy. The new generation of calcium antagonists could also be more effective in non-ischaemic cardiomyopathy. Although amlodipine significantly reduced mortality in the PRAISE trial in non-ischaemic cardiomyopathy, there was no favourable effect with felodipine in the V-HeFT-III tria. Finally, if in the earlier studies oral anticoagulants were more effective in non-ischaemic cardiomyopathy, the recent results of the SOLVD trial showed that warfarin decreased the mortality in both ischaemic and non-ischaemic cardiomyopathy. The value of anti-aggregant therapy is not questioned in coronary artery disease, but its role in dilated cardiomyopathy has not yet been established. In conclusion, apart from the use of digitalis which must be prudent in post-infarction cardiomyopathy or in patients with ventricular arrhythmias, the treatment of cardiac failure differs little with respect to its ischaemic or non-ischaemic aetiology, and should be based on the NYHA (New York Heart Association) classification.     

Does angiotensin-converting enzyme polymorphism influence the clinical manifestation and progression of heart failure in patients with dilated cardiomyopathy?

To evaluate the role of angiotensin-converting enzyme (ACE) polymorphism on the development of end-stage dilated cardiomyopathy, the ACE gene polymorphism of 90 patients after heart transplantation because of this disease was compared with the population sample. No difference in gene frequencies was found, but when compared with the population sample there were fewer ID heterozygotes detected; no significant influence of ACE polymorphism on the course of the disease before transplantation was found.     

A controlled study of the effects of carvedilol on clinical events, left ventricular function and proinflammatory cytokines levels in patients with dilated cardiomyopathy

BACKGROUND: Carvedilol is known to decrease the severity of ventricular dysfunction, to increase the left ventricular ejection fraction (LVEF), and, consequently, to reduce morbidity and mortality in patients with dilated cardiomyopathy. There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure. OBJECTIVE: To establish whether the addition of carvedilol has an additive beneficial effect on cytokines in patients with dilated cardiomyopathy who are already receiving treatment with angiotensin-converting enzyme (ACE) inhibitors, digoxin and diuretics. METHODS AND RESULTS: In this single-centre, prospective, randomized study, 60 patients with dilated cardiomyopathy with an LVEF less than 40% and already receiving digoxin, ACE inhibitors and diuretics for six months as the standard therapy were randomly assigned to receive either carvedilol (n=30) or placebo (n=30). Patients received an initial dosage of 3.125 mg carvedilol or placebo twice daily for two weeks, which was then increased at two-week intervals (if tolerated), first to 6.25 mg, then to 12.5 mg, and, finally, to a target dosage of 25 mg twice daily. Clinical examinations, radionuclide studies, and determinations of plasma levels of tumour necrosis factor-alpha (TNF-a), interleukin (IL)-2 and IL-6 were performed at baseline and repeated four months after random assignment. Primary end points were New York Heart Association functional class, LV function and plasma cytokines levels. Eight patients died (seven in the placebo group, P=0.05). Patients treated with carvedilol had a significant improvement in functional class compared with the baseline values (P=0.001), with a decrease in the levels of cytokines (IL-6 [P=0.001] and TNF-a [P=0.001]). LVEF increased from 22.14+/-7.85% to 27.85+/-11.80% (P=0.002), but diastolic function did not change in the carvedilol group. CONCLUSIONS: In patients with dilated cardiomyopathy, the addition of carvedilol to treatment with digoxin, ACE inhibitors and diuretics is associated with a significant improvement in symptoms and in LV function, and suppression of inflammatory cytokines.     

Inhibitory effect of captopril on cell degeneration and growth

Since the first administration of the angiotensin-converting enzyme (ACE) inhibitor captopril for the treatment of essential hypertension, it has been recognized that the ACE inhibitor has a positive influence on the cardiovascular system, on both a molecular and a clinical level.Over the past 25 years, the indications for ACE inhibitors have spread into many fields. During this period, interesting effects of ACE inhibitors in noncardiac fields have been reported. The present review outlines two studies regarding the protective effect of captopril on cardiomyopathy and its therapeutic effect on sarcoidosis.     

Astragalus polysaccharides inhibited diabetic cardiomyopathy in hamsters depending on suppression of heart chymase activation

Diabetic cardiomyopathy is associated with high morbidity and mortality of heart failure. Overactivation of the local chymase–Ang II system plays a dominant role in diabetic cardiomyopathy. Astragalus polysaccharide (APS) is used in traditional Chinese medicine to boost immunity. To study the effect of APS on local system of chymase-Ang II in diabetic cardiomyopathy, we investigated APS/normal saline (NS)-administrated streptozotocin-induced diabetic hamsters. After APS/NS administration at a dose of 1 g/kg per day for 10 weeks, hemodynamic parameters, levels of insulin (INS), C-peptide (C-P), glycosylated serum protein (GSP), lipoproteins, myocardial enzymes, and Ang II (plasma and myocardial) were tested; myocardial collagen (type I and III), myocardial ultrastructure, and activities of matrix metalloproteinase (MMPs) were measured; activities and expression of cardiac chymase and ACE were detected by using quantitative real-time RT-PCR and RIA; protein expression of cardiac phosphoric extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by Western blot. AP-administrated diabetic hamsters had lower levels of GSP, lipoproteins, myocardial enzymes, myocardial Ang II, expression of collagen I and I/ III, activities of pro-MMP-2 and MMP-2, activities and expression of chymase, and expression of p-ERK1/2 than NS-administrated diabetic hamsters and could better protect the myocardial ultrastructure. There was no difference in hemodynamic parameters between two groups. These results indicate that APS could inhibit diabetic cardiomyopathy in hamsters depending on the suppression of the local cardiac chymase–Ang II system.     

Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy is an inherited primary disorder of the myocardium characterised by clinical heterogeneity. The severity and rate of progression of hypertrophy is an important factor in prognosis, and is likely to be dependent on factors including age, the disease-causing gene mutation, environmental influences and genetic modifiers. METHODS: To study the influence of age on progression of hypertrophy, 62 patients with hypertrophic cardiomyopathy followed up for a minimum of 2 years were studied to determine the changes in left ventricular hypertrophy based on transthoracic M-mode and 2D echocardiography. DNA studies were performed to determine the role of the angiotensin-converting enzyme (ACE) gene deletion polymorphism in modulating progression of left ventricular hypertrophy. RESULTS: Sixty-two patients were followed-up over a period of 6.0 +/- 3.2 years (range 2-16 years). Patient data were analysed in two age groups: group 1 (patients aged < or = 30 years at first echocardiogram) had an increase in left ventricular septal wall thickness from 23.8 +/- 8.9 to 28.8 +/- 8.7 mm (p < 0.001), while group 2 (patients aged > 30 years) had a smaller but significant increase from 17.8 +/- 4.2 to 19.5 +/- 6.2 mm (p < 0.05). DNA analysis of the ACE gene deletion polymorphism showed those with the deletion/deletion (D/D) genotype had a greater progression of left ventricular hypertrophy compared to those carrying the other ACE genotypes (increase in hypertrophy: 6.2 +/- 3.3 vs. 1.7 +/- 4.2 mm; p < 0.01, D/D vs. I/D genotype; 2.8 +/- 5.8 mm; p = ns, D/D vs. I/I genotype). This association was independent of age, body mass and resting blood pressure. CONCLUSIONS: Progression of left ventricular hypertrophy is most evident in the first 3 decades of life, but is also observed in older age groups. Presence of the ACE gene D/D polymorphism may be an important marker to identify those individuals with hypertrophic cardiomyopathy who are likely to have more progressive disease, and therefore at higher risk of adverse clinical outcomes.     

血管紧张素转换酶2在肠道中作用的研究进展

血管紧张素转换酶2(ACE2)是人类ACE同源物,作为肾素-血管紧张素系统(RAS)中的关键酶,近年来受到广泛关注。诸多研究表明ACE2在糖尿病肾病、高血压、心力衰竭等疾病的病理生理过程中发挥重要作用,但其在肠道中的作用尚未完全明确。研究显示ACE2与肠道炎症关系密切,然而其具体作用尚存在争议。本文就ACE2在肠道中作用的研究进展作一综述。     

血管紧张素转化酶基因缺失多态性与肥厚型心肌病的关系

为探讨血管紧张素转化酶（ＡＣＥ）基因缺失／插入多态性与肥厚型心肌病（ＨＣＭ）发病的关系，对３５例ＨＣＭ患者进行了检测。结果证实ＡＣＥ基因缺失多态性与ＨＣＭ发病相关，并进一步发现前者还与左心室重量指数相关，为临床运用ＡＣＥ抑制剂治疗ＨＣＭ提供依据。