Chromogranin A: a novel susceptibility gene for essential hypertension

Abstract

Chromogranin A (CHGA) is ubiquitously expressed in secretory cells of the endocrine, neuroendocrine, and neuronal tissues. Although this protein has long been known as a marker for neuroendocrine tumors, its role in cardiovascular disease states including essential hypertension (EH) has only recently been recognized. It acts as a prohormone giving rise to bioactive peptides such as vasostatin-I (human CHGA(1-76)) and catestatin (human CHGA(352-372)) that exhibit several cardiovascular regulatory functions. CHGA is over-expressed but catestatin is diminished in EH. Moreover, genetic variants in the promoter, catestatin, and 3'-untranslated regions of the human CHGA gene alter autonomic activity and blood pressure. Consistent with these findings, targeted ablation of this gene causes severe arterial hypertension and ventricular hypertrophy in mice. Transgenic expression of the human CHGA gene or exogenous administration of catestatin restores blood pressure in these mice. Thus, the accumulated evidence establishes CHGA as a novel susceptibility gene for EH.

Molecular mechanism of interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor

“…It is generated from chromogranin A (CHGA) (Biswas et al, 2009;Helle, 2010), a major protein costored and co-released with catecholamines from secretory granules of chromaffin cells and adrenergic neurons (Sahu et al, 2010;Taupenot et al, 2003). Although CHGA is overexpressed in genetic hypertension (Friese et al, 2005;O'Connor et al, 1999;Takiyyuddin et al, 1995), the plasma CST level is diminished not only in established hypertensive patients but also in their normotensive offspring .…”

Catestatin Gly364Ser Variant Alters Systemic Blood Pressure and the Risk for Hypertension in Human Populations via Endothelial Nitric Oxide Pathway

“…Given that its precursor CHGA is a candidate gene for essential hypertension 47 , CST’s role as an anti-hypertensive agent has been an interesting topic of research. The primary evidence for this was found when the administration of exogenous CST resulted in the rescue of the hypertensive and hyperadrenergic phenotypes exhibited by CHGA knock-out mice 17, 48 .…”

Identification of the Vasoconstriction-Inhibiting Factor (VIF), a Potent Endogenous Cofactor of Angiotensin II Acting on the Angiotensin II Type 2 Receptor

“…22 Chromogranin A is a precursor protein for several biological active peptides with a vasoregulatory function such as vasostatin-I (human CHGA 1-97), [23][24][25] vasostatin-II (human CHGA 1-113), 25,26 and catestatin (human CHGA 352-372). 23,27 Vasostatin I and vasostatin II inhibit the vasoconstrictive effects of human vessels. 22 Vasostatin I is a regulator of adrenergic-induced cardiac inotropic effect.…”