Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 67, Issue 6, Pages 861-874Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0208-y
Keywords
Chromogranin A; Catestatin; Vasostatin; Cardiovascular; Blood pressure; Anti-hypertensive; Genetics; Hypertension
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Funding
- Center for Industrial Consultancy and Sponsored Research at IIT Madras
- Department of Biotechnology and Council for Scientific and Industrial Research, Govt. of India
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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.
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