Myocardial knockdown of mRNA-stabilizing protein HuR attenuates post-MI inflammatory response and left ventricular dysfunction in IL-10-null mice.

ABSTRACT: Prolonged inflammatory response is associated with left ventricular (LV) dysfunction and adverse remodeling following myocardial infarction (MI). IL-10 inhibits inflammation by suppressing HuR-mediated mRNA stabilization of proinflammatory cytokines. Here we report that following MI, IL-10(-/-) mice showed exaggerated LV dysfunction, fibrosis, and cardiomyocyte apoptosis. Short-hairpin RNA (shRNA)-mediated knockdown of HuR in the myocardium significantly reversed MI-induced LV dysfunctions and LV remodeling. HuR knockdown significantly reduced MI-induced cardiomyocyte apoptosis concomitant with reduced p53 expression. Moreover, HuR knockdown significantly reduced infarct size and fibrosis area, which in turn was associated with decreased TGF-beta expression. In vitro, stable knockdown of H

SUBMITTER: Krishnamurthy P 

PROVIDER: S-EPMC2887267 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature