Chromogranin A (CgA), a major component of the chromaffin granules, is co-stored and co-released with
catecholamines. It is also expressed in extra-adrenal sites, including the heart. In the rat, CgA localizes in atrial myoendocrine cells, associated with
Atrial Natriuretic Peptide (
ANP), and in the conduction system. In the human heart it is present in the ventricular myocardium, co-localized with B-type NP (BNP). CgA is the precursor of several biologically active
peptides generated by proteolytic processing also in the heart. Two of them,
vasostatin-1 (VS-1) and
catestatin (Cst), inhibit cardiac contraction and relaxation, counter-regulate beta-
adrenergic and endothelinergic stimulation, and protect the heart against
ischemia/
reperfusion damages. Recently, clinical studies have suggested CgA to be involved also in cardiovascular pathologies. High plasma CgA levels were found in
hypertension, chronic and acute
heart failure,
myocardial infarction, decompensated and hypertrophic heart, and
acute coronary syndromes. These alterations correlate with those of conventional cardiovascular
biomarkers, such as NP and
endothelin-1 (ET-1), and have prognostic relevance, being indicative of both severity of the disease and mortality. Accordingly, the current knowledge indicates CgA as a multifaceted
peptide in cardiovascular homeostasis. Whether the influence elicited by the
protein on both normal and failing heart is beneficial and/or detrimental, as well as its implication in the cardiac neuroendocrine scenario is under intense investigation. This review will focus on: i) the involvement of CgA and its derived
peptides in the mechanisms which sustain cardiac function and compensation, ii) CgA clinical relevance, and iii) its putative value as a clinical
biomarker.