Cardiac hypertrophy is an important mechanism by which the heart adapts to chronic increases in functional demands. Enhanced RNA and protein synthesis underly the increase in cardiac mass. Since the quality of proteins synthesized during hypertrophy determines the contractile performance of the myocardium, elucidation of transcriptional regulators is of primary importance. The proposed studies have as objective to examine the possible role of myocondial nuclear non-histone proteins in controlling RNA synthesis in the course of cardiac hypertrophy. Different models of hypertrophy will be studied: a) pressure-induced, following aortic constriction, b) volume-induced, following aorto-caval shunt, c) exercise-induced, and d) thyroxine-induced. The following parameters will be used: 1) heterogeneity of NHPs, 2) distribution of NHPs within myocyte chromatin subunits, 3) antigenic specificity, 4) posttranslational modifications, particularly phosphorylation, and 5) effects on in vitro RNA synthesis. It is hoped that these studies will define qualitative and quantitative changes in NHPs during the course of cardiac hypertrophy and elucidate the possible role of this nuclear fraction in myocardial RNA synthesis regulation.
NIH ExPorter
NIH ExPorter