Abstract 103: Role of miRNA-7 in Cardiac Function

Abstract

Studies in cancer have established clearly the role of epidermal growth factors receptors as targets of microRNA-7 (miR-7) but there are no studies so far to elucidate the role and function of miR-7 in human heart. Our studies show that ERBB2 (a member of epidermal growth factors receptor family) is targeted by miR-7 in human heart failure as well as in mice hearts undergoing stress. In order to understand the role of miR-7 in the heart, we generated miR-7 transgenic (Tg) mice with cardiac myocyte-specific overexpression of miR-7. miR-7 Tg mice have age dependent deterioration in cardiac dysfunction associated with cardiac dilation as measured by echocardiography (3 months - 60% FS, 6 month -52% FS and 12 months - 24%FS) and yet, they survive well for more than a year. To investigate whether pathological stress would accelerate the deterioration in cardiac function, miR-7 Tg mice were subjected to transverse aortic constriction (TAC) for two weeks. In contrast to the wild type littermates which undergo hypertrophic response following TAC, miR-7 Tg mice have accelerated cardiac dysfunction and dilation within two weeks. Histological analysis shows increased fibrosis in miR-7 Tg mice hearts as shown by Picro Sirius red and Meson Trichome staining which is further accelerated after TAC stress in hearts of the miR-7 Tg mice as compared to their sham controls. We also find that there is a difference in the mitochondrial morphology and structure in miR-7 Tg mice as compared to Wildtype controls as seen by transmission Electron Microscopy (TEM) explaining the reason for deteriorated cardiac function in terms of energy generation. Our study will discuss the mechanism underlying the deteriorated cardiac function in the miR-7 Tg mice after pathological stress as compared to wildtype littermates.