Chromogranin a and its fragments in cardiovascular, immunometabolic, and cancer regulation

Sushil K. Mahata, Angelo Corti

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Chromogranin A (CgA)—the index member of the chromogranin/secretogranin secretory protein family—is ubiquitously distributed in endocrine, neuroendocrine, and immune cells. Elevated levels of CgA-related polypeptides, consisting of full-length molecules and fragments, are detected in the blood of patients suffering from neuroendocrine tumors, heart failure, renal failure, hypertension, rheumatoid arthritis, and inflammatory bowel disease. Full-length CgA and various CgA-derived peptides, including vasostatin-1, pancreastatin, catestatin, and serpinin, are expressed at different relative levels in normal and pathological conditions and exert diverse, and sometime opposite, biological functions. For example, CgA is overexpressed in genetic hypertension, whereas catestatin is diminished. In rodents, the administration of catestatin decreases hypertension, cardiac contractility, obesity, atherosclerosis, and inflammation, and it improves insulin sensitivity. By contrast, pancreastatin is elevated in diabetic patients, and the administration of this peptide to obese mice decreases insulin sensitivity and increases inflammation. CgA and the N-terminal fragment of vasostatin-1 can enhance the endothelial barrier function, exert antiangiogenic effects, and inhibit tumor growth in animal models, whereas CgA fragments lacking the CgA C-terminal region promote angiogenesis and tumor growth. Overall, the CgA system, consisting of full-length CgA and its fragments, is emerging as an important and complex player in cardiovascular, immunometabolic, and cancer regulation.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
PublisherBlackwell Publishing Inc.
Pages34-58
Number of pages25
Edition1
DOIs
Publication statusPublished - Jan 1 2019

Publication series

NameAnnals of the New York Academy of Sciences
Number1
Volume1455
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Cancer
  • Cardiovascular diseases
  • Catestatin
  • Immunometabolism
  • Pancreastatin
  • Vasostatin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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