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Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh.

Abstract：

:Statins have recently been shown to produce anti-cardiac hypertrophic effects via the regulation of small GTPases. However, the effects of statins on G protein-mediated cardiac hypertrophy, which is the main pathway of cardiac hypertrophy, have not yet been studied. We sought to evaluate whether statin treatment directly suppresses cardiac hypertrophy through a large G protein-coupled pathway regardless of the regulation of small GTPases. Using neonatal rat cardiomyocytes, we evaluated norepinephrine-induced cardiac hypertrophy for suppressibility of rosuvastatin and the pathways involved by analyzing total protein/DNA content, cell surface area, immunoblotting and RT-PCR for the signal transduction molecule. In a concentration-dependent manner, rosuvastatin inhibited total protein synthesis and downregulated basal and norepinephrine-induced expressions of myosin light chain2 and the c-fos proto-oncogene in cardiomyocytes. Treatment with norepinephrine induced cardiac hypertrophy accompanied by G(h) expression and membrane translocation. Rosuvastatin inhibited G(h) protein activity in cardiomyocytes by inhibiting basal and norepinephrine-stimulated mRNA transcription, protein expression and membrane translocation; however, norepinephrine-stimulated G(q) protein expression was not inhibited. In addition, the norepinephrine-stimulated protein kinase C (PKC)-mitogen-activated protein kinase (MEK 1,2)-extracellular signal-regulated kinases (ERKs) signaling cascade was inhibited by pretreatment with rosuvastatin. Rosuvastatin treatment also helped maintain expression levels of SERCA2a and intracellular calcium concentration. G(h) protein is a novel target of statins in myocardial hypertrophy, and statin treatment may directly suppress cardiac hypertrophy through a large G(h) protein-coupled pathway regardless of the regulation of small GTPases.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Choi EY,Chang W,Lim S,Song BW,Cha MJ,Kim HJ,Choi E,Jang Y,Chung N,Hwang KC

doi

10.1016/j.ejphar.2009.10.050

subject

Has Abstract

pub_date

2010-02-10 00:00:00

pages

56-62

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(09)00957-1

journal_volume

627

pub_type

杂志文章

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Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh.