The involvement of Chromogranin A (CgA) in the cardiovascular function regulation is attributed to its function as a
prohormone. Several studies indicated that CgA-derived peptides, particularly Vasostatin-1 (VS-1) and Catestatin (CST), exert signaling
effects in numerous organs/systems, including the cardiovascular system.
This review focuses on the recently described signaling pathways activated by VS-1 and CST, giving insights into the mechanisms at the
basis of their cardiac negative inotropic action, their vasodilator effects and their cardioprotective role observed in different experimental
Accumulated evidences provided convincing support for VS-1 and CST as vasoactive peptides indirectly acting on cardiomyocytes
through a Ca2+-independent/PI3-K-dependent NO release from endothelial cells. This pathway is supposed to be triggered by the
interaction of these peptides with the plasma membrane. The premise of these studies grounds on the biochemical features of VS-1 and
CST, which are structurally characterized by amphipathic properties and the ability to interact with mammalian and microbial
membranes. On the other hand, recent data obtained in both isolated heart and isolated cardiomyocytes suggest that the VS-1 and CSTmediated
cardioprotective effects are primarily direct on the myocardium, rather than endothelium-dependent. Anyway, both direct and
indirect pathways seem to be characterized by the absence of specific membrane receptors on target cells, highlighting intriguing
novelties in the topic of cell signaling, in particular respect to an hypothetical receptor-independent eNOS activation.