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


METHODS
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.


CONCLUSIONS
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.
Ye
Ping
P
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China. yeping301@yahoo.com.cn
Sheng
Li
L
Zhang
Cheng
C
Liu
Yongxue
Y
D000818:Animals; D000069059:Atorvastatin; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006538:Heptanoic Acids; D047495:PPAR gamma; D011758:Pyrroles; D000069059:Atorvastatin