Biological function and clinical relevance of chromogranin A and derived peptides

Chromogranin A (CgA) is the major soluble protein co-stored and co-released with catecholamines and can function as prohromone giving rise to several bioactive peptides. This review focuses on these molecules summarizing their physiological functions, their pathogenetic implications and their recent use as biomarkers in several pathological conditions. A thorough literature search of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized key-words such Chromogranin A, Vasostatin-1 and 2, Chromofungin, Chromacin, Pancreastatin, Catestatin, WE-14, Chromostatin, GE-25, Parastatin and Serpinin, and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular and the immune systems and by affecting the glucose or calcium homeostasis. Since some peptides exert similar effects, but other elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenetic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumours, but also in cardiovascular, inflammatory and neuropsychiatric diseases