ACE2与新型冠状病毒肺炎

研究表明,血管紧张素转化酶(ACE)2很可能是2019新型冠状病毒(2019-nCoV)感染细胞的介导受体。ACE2在肺脏大多表达于Ⅱ型肺泡细胞,Ⅱ型肺泡细胞中ACE2的大量表达可能解释2019新型冠状病毒肺炎(COVID-19)中的肺部损伤。既往研究证实,ACE、血管紧张素Ⅱ、AngⅡ的高表达加重肺损伤,而ACE2对于肺损伤有保护作用,但目前尚无证据表明针对ACE及ACE2的治疗可有效缓解COVID-19。     

ACE2-Ang-（1—7）-Mas轴：心血管疾病治疗的新靶点

肾素一血管紧张素系统(RAS)在哺乳动物心血管活动的调节中发挥了重要的作用.随着血管紧张素转化酶(ACE)2和血管紧张素1-7[Ang-(1-7)]特异性受体Mas的发现,形成了RAS中一个对心血管有益的新分支:ACE2-Ang-(1-7)-Mas轴.其中ACE2可以水解血管紧张素Ⅰ(Ang Ⅰ)、血管紧张素Ⅱ(AngⅡ)生成Ang-(1-7).Ang-(1-7)则通过Mas受体拮抗AngⅡ的作用,引起血管舒张、抑制细胞增殖.这一新分支的发现为心血管疾病的治疗提供了新靶点.     

ACE2-Ang-(1-7)-MAS轴及其研究进展

肾素-血管紧张素系统(RAS)是一种经典的循环酶通路,研究证实,血管紧张素(Ang)Ⅱ是这一通路的重要代谢产物,在RAS中起重要生物学作用.血管紧张素转换酶2(ACE2)是新近发现的一种血管紧张素转换酶,该酶的主要转化产物为Ang1～Ang7[以下简写为 Ang-(l-7)]及其受体MAS,现就ACE2-Ang-(l-7)-MAS轴及其研究进展作一综述.     

ACE2--RAS代谢新通路在心血管活动调节中的作用

肾素-血管紧张素系统(RAS)在哺乳动物心血管活动调节中发挥着关键的作用。对RAS系统中血管紧张素转化酶(ACE)及血管紧张素Ⅱ(AngⅡ)的研究和认识已为临床治疗高血压、心力衰竭等心血管疾病提供了相当有效的帮助。近来,一种新的血管紧张素转化酶2(ACE2)被发现,ACE2的新的代谢通路对RAS系统传统代谢通路可能有着负性调节作用,ACE2代谢通路的发现为RAS系统的研究、认识心血管疾病发病机制和新药开发等开辟了全新的领域。     

ACE2-Ang(1-7)-Mas轴与心房颤动的关系

在肾素-血管紧张素系统(RAS)中,血管紧张素转化酶2(ACE2)与血管紧张素(AngⅡ)之间的代谢关系在ACE2-Ang(1-7)-Mas轴保护心房颤动(房颤)的心肌细胞作用中发挥着重要作用.作为ACE的唯一同系物,ACE2可以水解AngⅡ为七肽Ang(1-7),而Ang(1-7)可以特异性激活Mas受体,发挥抗纤维...     

奥美沙坦对肝纤维化大鼠血管紧张素转化酶2-血管紧张素(1-7)-Mas受体轴的影响

肾素-血管紧张素系统(renin-angiotensin system,RAS)是人类重要的生理功能调节系统,近年研究发现,RAS中血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)[血管紧张素(1-7) [angiotensin (1-7),Ang(1-7)]-Mas受体轴,可通过拮抗经典RAS作用轴延缓肝纤维化进程[1].血管紧张素Ⅱ受体拮抗剂(angiotensin Ⅱreceptor blocker,ARB)已证实具有抗肝纤维化作用,但其机制尚未完全明了.本研究通过观察奥美沙坦对肝纤维化大鼠肝脏ACE2-Ang(1-7)-Mas受体轴的影响,探讨其可能的抗肝纤维化机制.     

血管紧张素转移酶2-血管紧张素(1-7)-Mas轴在肾脏疾病发病机制中的作用

肾素-血管紧张素系统(RAS)过度兴奋,尤其是肾脏局部RAS高表达对肾脏疾病发生发展起重要作用.随着对RAS深入研究发现,除经典的RAS途径外,还有一条新的RAS途径:血管紧张素转移酶2-血管紧张素(1-7)-Mas轴[ACE2-Ang(1-7)-Mas轴],它和经典RAS相互作用,共同调节机体内环境稳定、维持肾脏功能正常.本文就ACE2-Ang(1-7)-Mas轴在肾脏生理及疾病中的作用及其机制做一简述.     

外周血ACE2及其抗体、Ang(1-7)与心力衰竭程度的关系

<正>近年发现新的肾素-血管紧张素(RAS)轴,即血管紧张素转化酶2-血管紧张素(1-7)-Mas系统。血管紧张素转化酶(ACE)2可有效地将血管紧张素(Ang)Ⅱ降解为Ang(1-7),后者与其受体Mas结合可拮抗AngⅡ的心脏毒性,通过改善心肌缺血再灌注后心肌的收缩功能,抑制AngⅡ诱导的心脏     

胰腺局部肾素-血管紧张素系统经典轴ACE-AngⅡ-AT1及新轴ACE2-Ang(1-7)-Mas的表达及意义

肾素-血管紧张素系统(RAS)是一种经典的循环酶通路,在胰腺功能活动调解中起着重要作用。近几年来随着人们对RAS的认识不断加深,发现RAS轴不仅包括经典轴ACE-AngⅡ-AT1轴,还包括新轴ACE2-Ang(1-7)-Mas轴。已有多项研究证实,ACE2-Ang(1-7)-Mas轴能对抗RAS经典轴的作用。综述了胰腺局部RAS两条轴各自的组成、功能及两者的比较分析。     

ACE2-Ang-（1—7）-Mas轴：心血管疾病治疗的新靶点

肾素-血管紧张素系统（RAS）在哺乳动物心血管活动的调节中发挥了重要的作用。随着血管紧张素转化酶（ACE）2和血管紧张素1—7[Ang-（1-7）]特异性受体Mas的发现,形成了RAS中一个对心血管有益的新分支：ACE2-Ang-（1-7）-Mas轴。其中ACE2可以水解血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅱ（AngⅡ）生成Ang-（1-7）。Ang（1-7）则通过Mas受体拮抗AngⅡ的作用,引起血管舒张、抑制细胞增殖。这一新分支的发现为心血管疾病的治疗提供了新靶点。     

ACE polymorphisms

Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.     

ACE and ACE2: a tale of two enzymes.

The cardiac renin–angiotensin–aldosterone system(RAAS) is an endocrine cascade, which results in the conversionof the inactive pro-hormone angiotensin I (Ang I) to the activepeptide hormone Ang II, and may also function as an autocrine/paracrinesystem to modulate cardiac function and growth. Renin, the initialenzyme of this cascade, cleaves the amino terminus of the pre-pro-hormoneangiotensinogen, thereby releasing the decapeptide pro-hormoneAng I. Angiotensin-converting enzyme (ACE) removes two additionalamino acids to yield the active octapeptide hormone Ang II.Ang II, acting through the AT1 receptor, is a potent vasoconstrictorand stimulates cardiac growth. This cardiac growth may be relatedto myocyte hypertrophy and/or fibroblast proliferation witha concomitant alteration in the extracellular matrix. Ang II,by interaction with the     

Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 ratio

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.     

ACE polymorphism and use of ACE inhibitors: effects on memory performance

Memory is an important cognition function, being fundamental to the development and independence of individuals. Our aim was to investigate the influence apolipoprotein E (APOE) and angiotensin I-converting enzyme (ACE) polymorphism and ACE inhibitors use, besides their interaction on memory performance of healthy subjects over 50 years. The sample consisted of 205 subjects assessed for five types of episodic memory, using Wechsler Memory Scale-Revised (WMS-R), who answered a questionnaire about drug use and were assessed for the ACE insertion/deletion polymorphism and APOE polymorphism. We found no influence of the APOE gene. The use of ACE inhibitors beneficially influenced learning ability scores (p = 0.02). Besides, I allele carriers of ACE polymorphism showed higher verbal memory scores compared with homozygous DD. Also, we observed an interaction influencing learning ability between the ACE polymorphism and the use of inhibitors, the beneficial influence of the I allele was present only in individuals who make use of ACE inhibitors. We conclude that the ACE gene has influence on memory performance, and that this influence is modulated by ACE inhibitors use.     

ACE Inhibitors and Chronotherapy

Chronotherapy can improve the effectiveness and reduce the adverse reactions of drugs and actually is used for several conditions including cardiovascular diseases. Although angiotensin converting enzyme (ACE) inhibitors are available for the therapy of patients with hypertension and/or heart failure, these agents have some characteristic adverse effects such as angioedema and dry cough. It has been reported that the dosing of ACE inhibitor at an inactive period has a better protective effect against cardiac hypertrophy in hypertensive rats, and changing dosing time from morning to evening reduces the severity and frequency of the drug-induced dry cough of hypertensive patients treated in the morning. Thus, the dosing of ACE inhibitors in the inactive span is more effective and safe. Dosing in the evening may be an alternative for hypertensives with dry cough with a morning dose of ACE inhibitors, if one ascertains that no circadian hyperamplitude tension is induced by the evening dose of this or any other antihypertensive drug.