The chromogranin A-derived peptides vasostatin-I and catestatin as regulatory peptides for cardiovascular functions.
A range of inflammatory conditions is associated with pathologically high levels of circulating chromogranin A (CgA). This prohormone belongs to the family of uniquely acidic proteins co-stored and co-secreted with other hormones and peptides from the diffuse neuroendocrine system. Two highly conserved, CgA-derived peptides, vasostatin-I and catestatin, have been implicated as modulators of a wide range of cells and tissues, including those of the cardiovascular system. This review focuses on links between elevated circulating CgA and cardiovascular dysfunctions in inflammatory conditions in relation to potential beneficial effects of vasostatin-I and catestatin. Characteristic membrane-penetrating properties have been assigned to both peptides, and pertussis toxin sensitivity is shared by a number of their responses, notably in the vascular and cardiac endothelium. Pertussis toxin-sensitive, receptor-independent activation via heterotrimeric G proteins and Galphai/o subunits will be discussed as possible mechanisms for inhibitory effects of vasostatin-I and catestatin on vascular and cardiac responses. The accumulated evidence provides convincing support for vasostatin-I and catestatin as regulatory peptides for the cardiovascular system, converging on alleviation of significant dysfunctions as part of several inflammatory conditions.