Improved cardiac performance by rosuvastatin is associated with attenuations in both myocardial tumor necrosis factor-alpha and p38 MAP kinase activity in rats after myocardial infarction.

Abstract

INTRODUCTION:

Statins have been shown to exert anti-inflammatory effects. The aim of this study was to investigate whether rosuvastatin has favorable effect on ventricular remodeling after myocardial infarction (MI), whether this effect is associated with tumor necrosis factor (TNF)-alpha expression and p38 mitogen-activated protein (MAP) kinase pathway and, furthermore, whether there is close correlation between gene expression of TNF-alpha and activity of p38 MAP kinase.

METHODS AND RESULTS:

Adult male Wistar rats with acute MI were randomly divided into 2 groups: (1) rosuvastatin-treated group (MI-R) receiving rosuvastatin 20 mg/kg once daily, and (2) infarcted group (MI) receiving saline, when compared with sham-operated control group. Four weeks later, echocardiography, hemodynamics and Van Gieson staining were applied to evaluate left ventricular remodeling and cardiac function. Myocardial gene expression of TNF-alpha and activity of p38 MAP kinase were analyzed by real time-polymerase chain reaction and Western blot, respectively. The results demonstrated that increased TNF-alpha gene expression in noninfarcted areas was accompanied by activation of p38 MAP kinase pathway. Moreover, treatment of rosuvastatin markedly improved ventricular remodeling and cardiac function in rats, which was associated with attenuations in both TNF-alpha gene expression and p38 MAP kinase activity in myocardium without changes in serum lipid levels.

CONCLUSIONS:

Treatment of rosuvastatin was able to improve cardiac remodeling and cardiac function after acute MI, which was associated with attenuations in both expression of TNF-alpha and activity of p38 MAP kinase in myocardium.

• Authors: Yingying Xu, Tingting Tang, Yingjun Ding, Rui Yao, Jiangjiao Xie, Mengyang Liao, Hong Xiao, Yong Chen, Xian Yu, Michael Fu, Yuhua Liao, Guanghong Zhao, Xiang Cheng
• Journal: The American journal of the medical sciences (Am J Med Sci) Vol. 340 Issue 2 Pg. 121-7 (Aug 2010) ISSN: 1538-2990 [Electronic] United States
• PMID: 20588182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipoproteins, HDL
• Lipoproteins, LDL
• Pyrimidines
• Sulfonamides
• Triglycerides
• Tumor Necrosis Factor-alpha
• Rosuvastatin Calcium
• Cholesterol
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Blood Pressure (drug effects, physiology)
• Blotting, Western
• Cholesterol (blood)
• Echocardiography
• Fluorobenzenes (pharmacology, therapeutic use)
• Heart (drug effects, physiopathology)
• Heart Rate (drug effects, physiology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Lipoproteins, HDL (blood)
• Lipoproteins, LDL (blood)
• Male
• Myocardial Infarction (drug therapy, pathology, physiopathology)
• Myocardium (chemistry, pathology)
• Pyrimidines (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Rosuvastatin Calcium
• Sulfonamides (pharmacology, therapeutic use)
• Triglycerides (blood)
• Tumor Necrosis Factor-alpha (analysis, biosynthesis)
• Ventricular Remodeling (drug effects, physiology)
• p38 Mitogen-Activated Protein Kinases (analysis, biosynthesis)