Premium
Inhibition of Angiotensin II‐Induced Cardiac Fibrosis by Atorvastatin in Adiponectin Knockout Mice
Author(s) -
Choi Sun Young,
Park Jong Sung,
Roh Mee Sook,
Kim ChongRak,
Kim Moo Hyun,
Serebruany Victor
Publication year - 2017
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-017-4246-1
Subject(s) - atorvastatin , ampk , angiotensin ii , endocrinology , adiponectin , medicine , protein kinase a , cardiac fibrosis , fibrosis , chemistry , statin , renin–angiotensin system , phosphorylation , receptor , biochemistry , diabetes mellitus , blood pressure , insulin resistance
Adiponectin is a polypeptide known to inhibit cardiac fibrosis via the activation of adenosine monophosphate‐activated protein kinase (AMPK). Statins can also activate AMPK, resulting in the secretion of adiponectin. We determined whether atorvastatin inhibits angiotensin II‐induced cardiac fibrosis (AICF) in the presence or absence of adiponectin. Adiponectin knockout (APN‐KO, n = 44) and wild type (WT, n = 44) mice were received subcutaneous angiotensin II (1.5 mg/kg/day), and atorvastatin (10 mg/kg/day) was administered orally for 15 days. The mRNA expression levels of collagen type I and III, as well as AMPK phosphorylation levels in cardiac tissue were then measured. In the APN‐KO mice, collagen type I ( p < 0.001) and type III ( p = 0.001) expression was significantly greater when treated with angiotensin II, while their expression was significantly reduced in the presence of angiotensin II and atorvastatin. Relative AMPK phosphorylation levels in APN‐KO mice were also significantly higher in the angiotensin II + atorvastatin group when compared with angiotensin II group alone. We conclude that atorvastatin attenuates AICF independently from adiponectin by activating AMPK. These data suggest potential cardioprotection beyond lipid modulation potentially supporting statin pleiotropic hypothesis.