Atorvastatin reverses cardiac remodeling possibly through regulation of protein kinase D/myocyte enhancer factor 2D activation in spontaneously hypertensive rats.

Abstract

The present study was designed to determine whether atorvastatin reduced hypertension-induced cardiac remodeling and whether these effects involved Protein Kinase D (PKD) and Myocyte Enhancer Factor 2D (MEF2D), factors known to be implicated in cardiac hypertrophy and fibrosis. 16-Week-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats were included. Blood pressure and serum lipid concentration were measured. H-E staining, myocardial transverse diameter, and echocardiography were examined to evaluate cardiac hypertrophy. Hydroxyproline content assay and Masson's trichrome staining were used to estimate cardiac fibrosis. Atorvastatin (10, 25 and 50mg/kg/day) was administered for 8 weeks. Increased blood pressure and cardiac remodeling were prominent in SHRs compared with WKY rats. SHRs also had elevated PKD and MEF2D activation. The systolic blood pressure, myocardial transverse diameter and hydroxyproline content were positively correlated with the activation level of PKD and MEF2D in SHRs. Atorvastatin significantly attenuated the activation of PKD and MEF2D. It may be concluded that atorvastatin reverses hypertension-induced cardiac remodeling partially through down-regulation of PKD/MEF2D activation. Our results predict novel therapeutic targets for atorvastatin in treating hypertensive patients.

• Authors: Jing Geng, Zhuo Zhao, Weiqiang Kang, Wei Wang, Yun Zhang, G E Zhiming
• Journal: Pharmacological research (Pharmacol Res) Vol. 61 Issue 1 Pg. 40-7 (Jan 2010) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 19683055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• MEF2 Transcription Factors
• MEF2D protein, rat
• Pyrroles
• Transcription Factors
• Atorvastatin
• protein kinase D
• Protein Kinase C
• Hydroxyproline

Topics

• Animals
• Atorvastatin
• Blood Pressure (drug effects)
• Disease Models, Animal
• Enzyme Activation
• Fibrosis
• Heptanoic Acids (pharmacology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Hydroxyproline (metabolism)
• Hypertension (complications, drug therapy, enzymology, physiopathology)
• Hypertrophy, Left Ventricular (drug therapy, enzymology, etiology, physiopathology)
• Lipids (blood)
• MEF2 Transcription Factors
• Male
• Myocardium (enzymology, pathology)
• Protein Kinase C (metabolism)
• Pyrroles (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Signal Transduction (drug effects)
• Time Factors
• Transcription Factors (metabolism)
• Ventricular Remodeling (drug effects)