Open AccessAngiotensin‐Converting Enzyme 3 ( ACE 3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy
Author(s) -
Yu ChangJiang,
Tang LiangLiang,
Liang Chen,
Chen Xiao,
Song ShuYing,
Ding XiaoQing,
Zhang KunYu,
Song BinLin,
Zhao Dan,
Zhu XueYong,
Li HongLiang,
Zhang ZhiRen
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.115.002680
Subject(s) - pressure overload , muscle hypertrophy , angiotensin ii , medicine , endocrinology , kinase , cardiac function curve , renin–angiotensin system , knockout mouse , signal transduction , protein kinase a , fibrosis , microbiology and biotechnology , heart failure , cardiac hypertrophy , blood pressure , biology , receptor
Background Angiotensin‐converting enzyme 3 ( ACE 3) is a recently defined homolog of ACE . However, the pathophysiological function of ACE 3 is largely unknown. Here, we aim to explore the role of ACE 3 in pathological cardiac hypertrophy. Methods and Results Neonatal rat cardiomyocytes ( NRCM s) with gain and loss of function of ACE 3 and mice with global knockout or cardiac‐specific overexpression of ACE 3 were used in this study. In cultured cardiomyocytes, ACE 3 conferred protection against angiotensin II (Ang II )‐induced hypertrophic growth. Cardiac hypertrophy in mice was induced by aortic banding ( AB ) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. Our data demonstrated that ACE 3‐deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac‐specific ACE 3‐overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that ACE 3‐mediated protection against cardiac hypertrophy by suppressing the activation of mitogen‐activated protein kinase kinase ( MEK )‐regulated extracellular signal‐regulated protein kinase ( ERK 1/2) signaling, which was further evidenced by the observation that inhibition of the MEK ‐ ERK 1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE 3‐deficient mice. Conclusions Our comprehensive analyses suggest that ACE 3 inhibits pressure overload‐induced cardiac hypertrophy by blocking the MEK ‐ ERK 1/2 signaling pathway.