摘要
心脏重构是多种心血管疾病终末期共同的病理表现,表现为心肌收缩和舒张功能障碍,射血分数不能满足全身组织器官代谢的需要,最终演变为心力衰竭。经典肾素-血管紧张素系统(RAS)即血管紧张素转化酶-血管紧张素Ⅱ-1型血管紧张素Ⅱ受体轴(ACE-AngⅡ-AT1R轴),其过度活化与心脏重构和心力衰竭的病理机制密切相关。血管紧张素转化酶2-血管紧张素(1-7)-Mas轴〔ACE2-Ang(1-7)-Mas轴〕是经典RAS的内源性负向调控通路,能拮抗和逆转AngⅡ对心脏的有害作用。ACE2是一种单羧肽酶,能在酶解AngⅡ的同时产生具有心脏保护效应的Ang(1-7)。Ang(1-7)主要通过其内源性受体Mas介导,发挥舒张血管、抑制细胞增殖分化、抗纤维化、抗血栓和逆转心脏重构的功能。随着近年来对ACE2-Ang(1-7)-Mas轴更深入的研究,对其代谢特点和作用机制有了更多的认识。本文对ACE2和Ang(1-7)在心脏重构及心力衰竭中的作用与相关机制进行了综述,并探讨了临床和实验研究中调控ACE2活性及Ang(1-7)水平在治疗心血管疾病中可能的获益,有望为这类疾病提供潜在的治疗方案。
Cardiac remodeling is a common pathological manifestation of various end-stage cardiovascular diseases,which leads to myocardial diastolic and systolic dysfunction,low ejection fraction which cannot meet the needs of systemic tissue and organ metabolism,and ultimate progress into heart failure.Excessive activation of the classical renin angiotensin system(RAS),which is the angiotensin-converting enzyme-angiotensinⅡ-type 1 angiotensinⅡreceptor axis(ACE2-AngⅡ-AT1R axis),plays a key role in the pathological process of cardiac remodeling and heart failure.Angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis[ACE2-Ang(1-7)-Mas axis]is an endogenous negative regulatory pathway of classical RAS,which can reduce its harmful effects.ACE2 is a monocarboxypeptidase that can hydrolyse AngⅡand produce Ang(1-7),which has cardio-protective effects.Ang(1-7),via endogenous receptor Mas,plays the role of vasodilating,anti-proliferation and anti-differentiation,anti-fibrosis,anti-thrombosis and reversing myocardial remodeling.In recent years,with increasingly growing studies on the ACE2-Ang(1-7)-Mas axis,there are more understanding about their metabolic characteristics and mechanism of action.This article describes the role of ACE2 and Ang(1-7)in cardiac remodeling and heart failure and the related mechanisms,and discusses the potential benefits by regulating ACE2 activity and Ang(1-7)levels in clinical and experimental studies,hopefully providing potential therapeutic strategies.
作者
杨吕
黄煜
何庆
Yang Lyu;Huang Yu;He Qing(Southwest Jiaotong University College of Medicine,Chengdu 610031,Sichuan,China;Department of Critical Care Medicine,the Third People's Hospital of Chengdu Affiliated to Southwest Jiaotong University,Chengdu 610000,Sichuan,China)
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2019年第11期1425-1428,共4页
Chinese Critical Care Medicine
基金
国家自然科学基金青年基金(81501640)
四川省成都市科技计划项目(2017FZ0058)。
