Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh

Eui Young Choi, Woochul Chang, Soyeon Lim, Byeong Wook Song, Min Ji Cha, Hye Jung Kim, Eunju Choi, Yangsoo Jang, Namsik Chung, Ki Chul Hwang

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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 Gh expression and membrane translocation. Rosuvastatin inhibited Gh protein activity in cardiomyocytes by inhibiting basal and norepinephrine-stimulated mRNA transcription, protein expression and membrane translocation; however, norepinephrine-stimulated Gq 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. Gh protein is a novel target of statins in myocardial hypertrophy, and statin treatment may directly suppress cardiac hypertrophy through a large Gh protein-coupled pathway regardless of the regulation of small GTPases.

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalEuropean Journal of Pharmacology
Volume627
Issue number1-3
DOIs
Publication statusPublished - 2010 Feb 10

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All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Choi, E. Y., Chang, W., Lim, S., Song, B. W., Cha, M. J., Kim, H. J., Choi, E., Jang, Y., Chung, N., & Hwang, K. C. (2010). Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh. European Journal of Pharmacology, 627(1-3), 56-62. https://doi.org/10.1016/j.ejphar.2009.10.050