Title:Chromogranin A and the Endothelial Barrier Function
VOLUME: 19 ISSUE: 24
Author(s):A. Corti and E. Ferrero
Affiliation:Division of Molecular Oncology, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy.
Keywords:Chromogranin A, vasostatin-1, TNF, NGR-TNF, VEGF, endothelial cell, vascular leakage, angiogenesis, VE-cadherin,
endothelial barrier function, cancer, neuroendocrine tumors.
Abstract:Chromogranin A (CgA) is an acidic glycoprotein belonging to a family of regulated secretory proteins stored in the dense core
granules of many neuroendocrine cells and neurons. This protein is produced, in certain conditions also by cardiomyocytes, keratinocytes
and granulocytes. Upon secretion CgA is released in the extracellular environment and then in circulation. Increased levels of circulating
CgA have been detected in patients with cancer, heart failure, hypertension, atrophic gastritis, renal failure, giant cell artheritis,
rheumatoid arthritis, sepsis and other inflammatory diseases. Endothelial cells, either those located in the close proximity of secretory
cells or in distant tissues, may be exposed, therefore, to variable levels of CgA. In this review we discuss recent findings that implicate
CgA and its fragments as a modulators of the physiology of endothelial cells in normal and in pathological conditions. In particular, we
review data that suggest that CgA and its N-terminal fragment, called vasostatin-1, are important modulators of the endothelial barrier
function and potent inhibitors of the endothelial cell activation caused by inflammatory and pro-angiogenic cytokines, with potential
implications in angiogenesis, inflammation and cancer.
