Biological function and clinical relevance of chromogranin A and derived peptides

Abstract

Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review 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 keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, 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. As some peptides exert similar effects, but others 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 pathogenic 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 tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.

The surging role of Chromogranin A in cardiovascular homeostasis

“…Therefore, CGA plasma levels have been used as prognostic indicators in these conditions (Helle et al, 2007; Angelone et al, 2012a; D'amico et al, 2014). It is important to note that pertinent information on plasma levels of CGA and its derived peptides can be best obtained by serological studies that in addition to processing-independent radioimmunoassays include also region-specific processing-dependent assays.…”

Cromogranina A e peptidi derivati: fisiopatologia e importanza clinica

“…Infatti, la proprietà della CgA di legare gli ioni calcio con alta capacità, ma con bassa affinità va a determinare all'interno del granulo un compartimento ad alta concentrazione di calcio che, tuttavia, diviene prontamente disponibile come messaggero a livello citoplasmatico (attraverso l'apertura, recettore mediata e inositol-3 fosfato dipendente, di specifici canali posti sulla membrana granulare) [4,5].…”

The Monocyte-to-Lymphocyte Ratio Correlates with Psycho-Neuro-Inflammatory Factors in Patients with Stable Coronary Artery Disease

“…The sympathetic-adrenomedullary system and the hypothalamic-pituitary-adrenocortical (HPA) axis critically govern the stress response. To some extent, plasma cortisol levels indicate HPA axis activity and plasma chromogranin A (CgA) levels reflect neuroendocrine and sympathoadrenal activity [8,9]. …”