This Article Full Text (OnlineFirst PDF) All Versions of this Article: 1074248409344329v1 14/4/283    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Kang, B.-Y. Articles by Mehta, J. L. PubMed PubMed Citation Articles by Kang, B.-Y. Articles by Mehta, J. L. Social Bookmarking                         What's this?

Rosuvastatin Attenuates Ang II–Mediated Cardiomyocyte Hypertrophy via Inhibition of LOX-1

University of Arkansas for Medical Sciences, Little Rock, Arkansas; Central Arkansas Veterans Healthcare System, Little Rock, Arkansas

^* To whom correspondence should be addressed. E-mail: mehtajl{at}uams.edu.

	Abstract

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, also known as statins, have been shown to reduce cardiac remodeling. Angiotensin II (Ang II) type 1 receptor (AT1R) and oxidized low-density lipoprotein (ox-LDL) via its lectin-like ox-LDL receptor (LOX-1) are major stimuli for cardiomyocyte growth. We postulated that rosuvastatin, a potent HMG-CoA reductase inhibitor, may reduce Ang II–mediated cardiomyocyte growth via AT1R and LOX-1 inhibition. HL-1 adult mouse cardiomyocytes were incubated overnight in serum-free medium, and then treated with rosuvastatin, the AT1R inhibitor losartan or anti-LOX-1 antibody for 3 hours. The cells were then stimulated with Ang II. We measured cardiomyocyte growth, and associated intracellular redox signals using reverse transcription–polymerase chain reaction (RT-PCR) and real-time quantitative PCR. Losartan and anti-LOX-1 antibody markedly attenuated Ang II–mediated oxidant stress, and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p40^ph°^x and gp91^ph°^x subunits) and nuclear factor-B (NF-B). Rosuvastatin attenuated the Ang II–mediated upregulation of both subunits of NAPDH oxidase as well as NF-B. Rosuvastatin also reduced Ang II–mediated upregulation of AT1R and LOX-1. In other experiments, LOX-1 was upregulated in cardiomyocytes by transfection with pCI-neo/LOX-1, which also enhanced the expression AT1R messenger RNA (mRNA), and rosuvastatin pretreatment reduced the expression of both LOX-1 and AT1R in this system. Thus, rosuvastatin attenuates Ang II–mediated cardiomyocyte growth by inhibiting LOX-1 and AT1R expression and suppressing the heightened intracellular redox state.

First published on September 1, 2009, doi:10.1177/1074248409344329

Journal of Cardiovascular Pharmacology and Therapeutics 2009;14:283.

A more recent version of this article appeared on December 1, 2009


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?