Atorvastatin attenuating down-regulation of peroxisome proliferator-activated receptor gamma in preventing cardiac hypertrophy of rats in vitro and in vivo.

Abstract

PURPOSE:

To investigate whether the role of atorvastatin in suppression of cardiac hypertrophy is potentially associated with the change of peroxisome proliferator-activated receptor gamma (PPARgamma) expression, and the anti-inflammatory effect in vitro and in vivo.

METHOD:

Cardiac hypertrophy was established by angiotensin II in neonatal cardiac myocytes in vitro and incomplete ligation of abdominal aorta of SD rats in vivo. PPARgamma and cytokines mRNA expression was evaluated by RT-PCR, and the rate of protein synthesis in cardiac myocytes by 3H-leucine incorporation.

RESULTS:

Atorvastatin attenuated downregulation of PPARgamma mRNA and inhibited brain natriuretic peptide (BNP), interleukin-1beta (IL-1beta) and matrix metalloproteinase 9 (MMP9) mRNA expression, as well as 3H-leucine incorporation in a dose-dependent manner in vitro. Furthermore, atorvastatin reduced the mRNA expression of BNP, IL-1beta and MMP9, and enhanced PPARgamma mRNA expression, and diminished the pressure overload-induced increase in the ratio of heart weight to body weight, left ventricular wall thickness and myocyte diameter of rats in vivo.

CONCLUSION:

Atorvastatin prevents cardiac hypertrophy of rats, probably associated with the modulation of PPARgamma and the inhibition of myocardial inflammation. Atorvastatin may play a role in prevention and treatment of cardiovascular diseases characterized by cardiac hypertrophy.

• Authors: Ping Ye, Li Sheng, Cheng Zhang, Yongxue Liu
• Journal: Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques (J Pharm Pharm Sci) Vol. 9 Issue 3 Pg. 365-75 ( 2006) ISSN: 1482-1826 [Electronic] Switzerland
• PMID: 17207419 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heptanoic Acids
• PPAR gamma
• Pyrroles
• Atorvastatin

Topics

• Animals
• Atorvastatin
• Cells, Cultured
• Down-Regulation (drug effects, physiology)
• Heptanoic Acids (pharmacology)
• Hypertrophy, Left Ventricular (metabolism, pathology, prevention & control)
• Male
• PPAR gamma (antagonists & inhibitors, metabolism)
• Pyrroles (pharmacology)
• Rats
• Rats, Sprague-Dawley