Abstract 320: Roles of Estrogen, AMPK and Micro RNAs in the Progression of Cardiac Hypertrophy
In industrialized countries, the prevalence of congestive heart failure (CHF) is increasing steadily and has become one of the leading causes of hospitalization. In addition, the risk of cardiovascular disease increases in post-menopausal women. Yet, the association between estrogen and the risk of CHF has not been adequately studied. Recently, MicroRNAs (miR) and AMP-kinase (AMPK) have emerged as prominent players in the development of cardiac hypertrophy and heart failure. Our on-going studies indicate differential AMPK regulation through two miR species (miR195 and miR451) in a mouse model harboring a missense mutation (R403Q) in alpha-myosin heavy chain (αMHC) causing hypertrophic cardiomyopathy (HCM). Using bioinformatic algorithms (TargetScanMouse, 5.2), we were able to predict miR candidates that potentially target the AMPK axis. In addition, Altered expression of miRs that target AMPK axis was found in phenylephrine induced hypertrophic neonatal rat cardiomyocytes (NRCM). However, Estradiol treatment of NRCM blocked the hypertrophic changes induced by phenylephrine treatment. It was known that the activation of AMPK pathway inhibits cardiomyocyte hypertrophy. Our data showed that AMPK pathway was activated by Estradiol treatment, which can be blocked by estrogen receptor (ER) β antagonist. Therefore, estradiol increase AMPK pathway activation which in turn attenuate phenylephrine induced increase in cardiomyocyte cell size. Further studies are need to further explore the role of estrogen in the regulation of miR expression in hypertrophic cardiomyocytes, and the role of the expression changes of miRs regulated by estrogen in the development of hypertrophic phenotype.
- © 2013 by American Heart Association, Inc.