

FOLLOWUS
1Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China
2Department of Pharmacology & Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China;
*Corresponding author Tel: 86-10-88626575, Fax: 86-10-88270497, E-mail: yeping301@yahoo.com.cn
Published Online:20 August 2015,
Published:2015-08
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Sheng Li, Yang Xu, Ye Ping, et al. Effect of Atorvastatin on Expression of Peroxisome Proliferator-activated Receptor Beta/delta in Angiotensin Ⅱ-induced Hypertrophic Myocardial Cells
Objective
To explore the effect of atorvastatin on cardiac hypertrophy and to determine the potential mechanism involved.
Methods
An
in vitro
cardiomyocyte hypertrophy from neonatal rats was induced with angiotensinⅡ (Ang Ⅱ) stimulation. Before AngⅡ stimulation
the cultured rat cardiac myocytes were pretreated with atorvastatin at different concentrations (0.1
1
and 10 μmol/L). The following parameters were evaluated: the myocyte surface area
3
H-leucine incorporation into myocytes
mRNA expressions of atrial natriuretic peptide
brain natriuretic peptide
matrix metalloproteinase 9
matrix metalloproteinase 2
and interleukin-1β
mRNA and protein expressions of the δ/β peroxisome proliferator-activated receptor (PPAR) subtypes.
Results
It was shown that atorvastatin could ameliorate Ang Ⅱ-induced neonatal cardiomyocyte hypertrophy in the area of cardiomyocytes
3
H-leucine incorporation
and the expression of atrial natriuretic peptide and brain natriuretic peptide markedly. Meanwhile
atorvastatin also inhibited the augmented mRNA level of several cytokines in hypertrophic myocytes. Furthermore
the down-regulated expression of PPAR- δ/β at both the mRNA and protein levels in hypertrophic myocytes could be significantly reversed by atorvastatin treatment.
Conclusions
Atorvastatin could improve AngⅡ-induced cardiac hypertrophy and inhibit the expression of cytokines. Such effect might be partly achieved through activation of the PPAR-δ/β pathway.
1.Levy D , Garrison RJ , Savage DD , et al . Prognostic implications of echocardiographically determined left- ventricular mass in the Framingham-heart-study. N Engl J Med 1990 ; 322 : 1561 - 6 .
2 . Lorell BH, Carabello BA. Left ventricular hypertrophy- pathogenesis, detection, and prognosis. Circulation 2000 ; 102 : 470 - 9 .
3 . Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure. N Engl J Med 1999 ; 341 : 1276 - 83 .
4.Harada E , Nakagawa O , Yoshimura M , et al . Effect of interleukin-1β on cardiac hypertrophy and production of natriuretic peptides in rat cardiocyte culture. J Mol Cell Cardiol 1999 ; 31 : 1997 - 2006 .
5.Sakata Y , Yamamoto K , Mano T , et al . Activation of matrix metalloproteinases precedes left ventricular remodeling in hypertensive heart failure rats: its inhibition as a primary effect of angiotensin-converting enzyme inhibitor. Circulation 2004 ; 109 : 2143 - 9 .
6 . Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005 ; 54 : 2460 - 70 .
7.Irukayama-Tomobe Y , Miyauchi T , Sakai S , et al . Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-alpha partly via blockade of c-Jun NH2-terminal kinase pathway. Circulation 2004 ; 109 : 904 - 10 .
8.Planavila A , Rodriguez-Calvo R , Jove M , et al . Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc Res 2005 ; 65 : 832 - 41 .
9.Hayashidani S , Tsutsui H , Shiomi T , et al . Fluvastatin, a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 2002 ; 105 : 868 - 73 .
10.Nishikawa H , Miura S , Zhang B , et al . Statins induce the regression of left ventricular mass in patients with angina. Circ J 2004 ; 68 : 121 - 5 .
11 .Simpson P, McGrath A, Savion S. Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines. Circ Res 1982 ; 51 : 787 - 801 .
12 .Simpson P, Savion S. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyo- cardial cells. Circ Res 1982 ; 50 : 101 - 16 .
13.Thaik CM , Calderone A , Takahashi N , et al . Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes. J Clin Invest 1995 ; 96 : 1093 - 9 .
14.Takemoto M , Node K , Nakagami H , et al . Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001 ; 108 : 1429 - 37 .
15 .Porter KE, Turner NA, O’Regan DJ. Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA. Cardiovasc Res 2004 ; 61 : 745 - 55 .
16.Frey N , Katus HA , Olson EN , et al . Hypertrophy of the heart: a new therapeutic target? Circulation 2004 ; 109 : 1580 - 9 .
17.Patel R , Nagueh SF , Tsybouleva N , et al . Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 2001 ; 104 : 317 - 24 .
18.Ye P , Fang H , Zhou X , et al . Effect of peroxisome proliferator-activated receptor activators on tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes. Chin Med J Sci 2004 ; 19 : 243 - 7 .
19.Ding G , Cheng L , Qin Q , et al . PPAR delta modulates lipopolysaccharide-induced TNF alpha inflammation signaling in cultured cardiomyocytes. J Mol Cell Cardiol 2006 ; 40 : 821 - 8 .
20.Zhang H , Shao Z , Alibin CP , et al . Liganded peroxisome proliferator-activated receptors (PPARs) preserve nuclear histone deacetylase 5 levels in endothelin-treated Sprague-Dawley rat cardiac myocytes. PLoS One 2014 ; 9 : e115258 .
21 .Paumelle R, Staels B. Cross-talk between statins and PPAR alpha in cardiovascular diseases: clinical evidence and basic mechanisms. Trends Cardiovasc Med 2008 ; 18 : 73 - 8 .
22 .Lee TM, Chou TF, Tsai CH. Association of pravastatin and left ventricular mass in hypercholesterolemic patients: role of 8-iso-prostaglandin F2a formation. J Cardiovasc Pharmacol 2002 ; 40 : 868 - 74 .
23.Inoue I , Goto S , Mizotani K , et al . Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyc- looxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary endothelial cells. Life Sci 2000 ; 67 : 863 - 76 .
24.Desjardins F , Sekkali B , Verreth W , et al . Rosuvastatin increases vascular endothelial PPAR-γ expression and corrects blood pressure variability in obese dyslipidaemic mice. Eur Heart J 2008 ; 29 : 128 - 37 .
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