title: Angiotensin-Converting Enzyme 3 (ACE3) Protects Against Pressure Overload-Induced Cardiac Hypertrophy.
abstract: BACKGROUND
  Angiotensin-converting enzyme 3 (ACE3) is a recently defined homolog of ACE. However, the pathophysiological function of ACE3 is largely unknown. Here, we aim to explore the role of ACE3 in pathological cardiac hypertrophy.
  
  
  RESULTS
  Neonatal rat cardiomyocytes (NRCMs) with gain and loss of function of ACE3 and mice with global knockout or cardiac-specific overexpression of ACE3 were used in this study. In cultured cardiomyocytes, ACE3 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 ACE3-deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac-specific ACE3-overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that ACE3-mediated protection against cardiac hypertrophy by suppressing the activation of mitogen-activated protein kinase kinase (MEK)-regulated extracellular signal-regulated protein kinase (ERK1/2) signaling, which was further evidenced by the observation that inhibition of the MEK-ERK1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE3-deficient mice.
  
  
  CONCLUSIONS
  Our comprehensive analyses suggest that ACE3 inhibits pressure overload-induced cardiac hypertrophy by blocking the MEK-ERK1/2 signaling pathway.
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Tang
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Song
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Ding
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Kun-Yu
authors.initials: KY
authors.lastname: Zhang
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China.
authors.forename: Bin-Lin
authors.initials: BL
authors.lastname: Song
authors.affiliation: Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Xue-Yong
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, China Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, China Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China zhirenz@yahoo.com.
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000503:physiopathology / Q000601:surgery; D062186:Arterial Pressure; D006332:Cardiomegaly / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005355:Fibrosis; D008026:Ligation; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection
chemical_list: D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C522402:Ace3 protein, mouse; D007703:Peptidyl-Dipeptidase A; C000612092:angiotensin converting enzyme 3, rat
keywords: ERK1/2; MEK1/2; angiotensin‐converting enzyme 3; cardiac hypertrophy; signaling pathway