Abstract 5442: Oxidative Stress Regulates Cardiac Stem Cell Differentiation in a MicroRNA-Mediated Mechanism

TL;DRAbstract

Oxidative stress, specifically hydrogen peroxide (H 2 O 2 ) is significantly increased following myocardial infarction and its effect on adult cardiac stem cell (CSC) differentiation is largely unknown. To promote endogenous and implanted CSC differentiation into functional cardiac cells in ischemic tissue, mechanisms of deleterious redox signaling on cardiomyogenesis must be determined. Our data demonstrate that H 2 O 2 time- and dose-dependently inhibits Nkx2.5 expression in CSCs exposed to differentiating medium. Since overexpression of microRNA (miR)-1 increases embryonic stem cell cardiac differentiation, we hypothesized that H 2 O 2 regulates CSC differentiation in a miRNA-mediated mechanism. CSCs exposed to H 2 O 2 (1–100 μ M) in differentiating media demonstrated time-dependent, decreased expression of miR1 compared to cells exposed to differentiating media alone (1 μ M: 37±7.6% decrease from Day 5 control; 100 μ M: 47±11% decrease from Day 8 control). MiR133a, essential for no

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