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Simvastatin exerts cardioprotective effects and inhibits the activity of R ho‐associated protein kinase in rats with metabolic syndrome
Author(s) -
Li ChuanBao,
Li XiaoXing,
Chen YuGuo,
Gao HaiQing,
Bao MeiCheng,
Zhang Juan,
Bu PeiLi,
Zhang Yun,
Ji XiaoPing
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05730.x
Subject(s) - simvastatin , protein kinase b , medicine , insulin resistance , endocrinology , rho associated protein kinase , phosphatidylinositol , chemistry , kinase , phosphorylation , pi3k/akt/mtor pathway , phosphatase , pharmacology , signal transduction , insulin , biochemistry
Summary Insulin resistance ( IR ) is crucially involved in the pathophysiology of metabolic syndrome ( MS ). The aim of the present study was to investigate the effects of simvastatin on IR in rats with MS . A rat model of MS was established and myocardial damage was examined by transmission electron microscopy. Twenty‐two MS rats were divided into two groups of 11 rats each: (i) an MS group; and (ii) a simvastatin‐treated MS . Ten Wistar rats were used as controls. The phosphorylation of myosin phosphatase target subunit 1 ( MYPT ‐1), insulin receptor substrate 1 ( IRS ‐1) and A kt were analysed by immunohistochemistry and western blotting. Insulin resistance‐induced MS was associated with a significant increase in R ho kinase ( ROCK ) activity and inhibition of the phosphatidylinositol 3‐kinase ( PI 3‐K)/Akt pathway. Decreased levels of phosphorylated (p‐) MYPT ‐1 and p‐ IRS ‐1 (Ser 307 ) and increased levels of p‐Akt were found in hearts from the MS + simvastatin compared with the MS group. These results suggest that simvastatin reduces ROCK activity and increases A kt activity. Simvastatin exerts cardioprotective effects and improves IR , which can be attributed, at least in part, to the inhibition of ROCK and activation of PI 3‐K/ A kt.