Abstract 360: PKA is Needed for Acute Adaptation for Cardiac Stress

Abstract

In adult mammalian hearts, the ventricles are composed of mostly binucleated myocytes (BVMs) and some mononucleated myocytes (MVMs), which have different properties. However, if the gene expression profile and pathological responses of these two populations of myocytes are different have not reported. We found that these two populations of myocytes differentially expressed 250 genes. While many RNA synthesis and processing genes, and some antiapoptotic genes were highly expressed in MVMs, BVMs had genes related to self-destruction (autophagy and ubiquitination system genes) enriched. In general, expression of genes involved in carbonhydrate metabolism and cell proliferation was also more but the expression of genes involved in fatty acid metabolism was less in MVMs. The expression of some of these genes was confirmed in single-molecule pulldown (SiMPull) method in separated MVMs and BVMs. MVMs grew more in pressure overloaded hearts. MVMs were more resistant to apoptosis induced by β-adrenergic stimulation both in vitro and in vivo , which was due to cytosolic and mitochondrial Ca 2+ and ROS could be more easily increased in BVMs leading to more damage to mitochondria. Ca 2+ current, myocyte contraction and Ca 2+ transients in MVMs had less responses to β-adrenergic stimulation (isoproterenol, 1uM). Furthermore, MVMs gene expression upon β-adrenergic stimulation showed more adaptive responses while BVMs showed more proapoptotic gene (e.g., p53 and AIF), protein post-translational modification and muscle differentiation gene expression. This study suggests that MVMs and BVMs are distinct subpopulations of VMs with different gene expression profile and pathological responses. It underscores the importance of differential pathological responses of cells having different nuclear numbers .