UC San Diego

Chromogranin A (CGA), a 48-kDa polypeptide, is a index member of the chromogranin/secretogranin family of proteins. CGA is widely distributed in the endocrine and neuroendocrine systems and is co-stored and co-released with catecholamines in the adrenal medulla. Although CGA has generally been associated with the neuroendocrine system, recent studies have shown that CGA is expressed in human heart and may play a direct role in regulating cardiovascular system. Studies in our laboratory have shown that CGA knockout mice have high blood pressure and show cardiac enlargement. Furthermore, elevated plasma levels of CGA protein have been observed in patients with fatal heart diseases, including chronic heart failure and acute myocardial infarction. At present, the role of CGA in cardiac ischemic reperfusion injury has remained elusive. Our findings demonstrate for the first time that CGA is cardioprotective against ischemic reperfusion injury and mediates its cardioprotective effect by activation of a Gi/Go pathway utilizing in vivo and in vitro approaches