Simvastatin exerts cardioprotective effects and inhibits the activity of Rho-associated protein kinase in rats with metabolic syndrome.

Abstract

1. 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. 2. 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 Akt were analysed by immunohistochemistry and western blotting. 3. Insulin resistance-induced MS was associated with a significant increase in Rho kinase (ROCK) activity and inhibition of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Decreased levels of phosphorylated (p-) MYPT-1 and p-IRS-1 (Ser³⁰⁷) 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 Akt activity. 4. Simvastatin exerts cardioprotective effects and improves IR, which can be attributed, at least in part, to the inhibition of ROCK and activation of PI3-K/Akt.

• Authors: Chuan-Bao Li, Xiao-Xing Li, Yu-Guo Chen, Hai-Qing Gao, Mei-Cheng Bao, Juan Zhang, Pei-Li Bu, Yun Zhang, Xiao-Ping Ji
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 39 Issue 9 Pg. 759-64 (Sep 2012) ISSN: 1440-1681 [Electronic] Australia
• PMID: 22670687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

Chemical References

• Cardiotonic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Insulin Receptor Substrate Proteins
• Irs1 protein, rat
• Simvastatin
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• rho-Associated Kinases
• Ppp1r12a protein, rat
• Protein Phosphatase 1

Topics

• Animals
• Cardiotonic Agents (therapeutic use)
• Heart (drug effects, physiopathology)
• Heart Diseases (etiology, metabolism, physiopathology, prevention & control)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Insulin Receptor Substrate Proteins (agonists, metabolism)
• Insulin Resistance
• Male
• Metabolic Syndrome (drug therapy, metabolism, pathology, physiopathology)
• Mitochondrial Swelling (drug effects)
• Myocardium (enzymology, metabolism, ultrastructure)
• Phosphatidylinositol 3-Kinase (chemistry, metabolism)
• Phosphorylation (drug effects)
• Protein Phosphatase 1 (metabolism)
• Protein Processing, Post-Translational (drug effects)
• Proto-Oncogene Proteins c-akt (agonists, metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Simvastatin (therapeutic use)
• Vacuoles (drug effects, ultrastructure)
• rho-Associated Kinases (antagonists & inhibitors, metabolism)