Cardioprotection against ischemia/reperfusion injury and chromogranin A derived peptides

Chromogranin A (CgA) is produced by cells of the sympathoadrenal system and by human ventricular myocardium. In the clinical setting CgA has been mainly used as a marker of neuroendocrine tumors, but in the last decade a plenty of data have been published on the role of CgA and its derived peptides, particularly catestatin and vasostatin, in the regulation of cardiovascular function and diseases, including heart failure and hypertension. CgA-derived peptides, namely catestatin and vasostatin, may exert negative inotropic and lusitropic effects on mammalian hearts. As such CgA and its derived peptides may be regarded as mediators of a complex feedback system able to modulate the exaggerated release of catecholamines. This system may be also interpreted as an attempt for compensatory cardioprotective response against myocardial injury in the pre and postischemic scenarios. In fact, while vasostatin can trigger cardioprotective effects akin ischemic preconditioning (protection is triggered before ischemia), catestatin is a potent cardioprotective agent in the early post-ischemic phase, acting like a postconditioning agent (protection is triggered at the onset of reperfusion). Admittedly, the exact mechanism of cardioprotection of this system is far from being fully understood. Interestingly, both vasostatin and catestatin have shown to be able to activate multiple cardioprotective pathways. In particular, these two CgA-derived peptides may induce nitric oxide dependent pathway, which may play a pivotal role in cardioprotection against ischemia/reperfusion injury. Here, we review the literature about the cardiac effects of catestatin and vasostatin, the mechanisms of myocardial injury and protection and the role of CgA derived peptides in cardioprotection.