Molecular and Cellular Mechanisms of Action of CgA-Derived Peptides in Cardiomyocytes and Endothelial Cells

Abstract

Several studies indicate that Chromogranin A (CgA)-derived peptides, in particular Vasostatin-1 (VS-1), Catestatin (CST), Chromofungin and Serpinin, exert important regulatory effects in numerous organs/systems, including the cardiovascular system. This chapter focuses on the recently discovered signalling pathways activated by CgA-derived peptides in cardiomyocytes and endothelial cells, giving insights into the mechanisms at the basis of their inotropic and cardioprotective effects. Several evidences provided convincing support for VS-1 and CST as cardiac inotropic peptides, indirectly acting on cardiomyocytes through a Ca2+-independent/PI3K-dependent NO release from endothelial cells. This pathway appears to be triggered by the interaction of these peptides with the plasma membrane, as suggested by the biochemical features of VS-1 and CST, structurally characterized by amphipathic properties, and their ability to interact with mammalian and microbial membranes. However, recent data suggest that both VS-1 and CST are also able to exert direct cardioprotective effects in isolated cardiomyocytes, independently from the presence of endothelial cells. Interestingly, both direct and indirect effects seem to be characterized by the absence of specific membrane receptors on target cells, highlighting intriguing novelties in the topic of cell signalling, in particular respect to an hypothetical receptor-independent eNOS activation.