Endothelium Dependent Cardiovascular Effects of the Chromogranin A-Derived Peptides Vasostatin-1 and Catestatin
Authors: Fornero, S.; Bassino, E.; P. Gallo, M.; Ramella, R.; Levi, R.; Alloatti, G.
Source: Current Medicinal Chemistry, Volume 19, Number 24, August 2012 , pp. 4059-4067(9)
Publisher: Bentham Science Publishers
Abstract:The involvement of Chromogranin A (CgA) in the cardiovascular function regulation is attributed to its function as a prohormone. Several studies indicated that CgA-derived peptides, particularly Vasostatin-1 (VS-1) and Catestatin (CST), exert signaling effects in numerous organs/systems, including the cardiovascular system.
This review focuses on the recently described signaling pathways activated by VS-1 and CST, giving insights into the mechanisms at the basis of their cardiac negative inotropic action, their vasodilator effects and their cardioprotective role observed in different experimental conditions.
Accumulated evidences provided convincing support for VS-1 and CST as vasoactive peptides indirectly acting on cardiomyocytes through a Ca2+-independent/PI3-K-dependent NO release from endothelial cells. This pathway is supposed to be triggered by the interaction of these peptides with the plasma membrane. The premise of these studies grounds on the biochemical features of VS-1 and CST, which are structurally characterized by amphipathic properties and the ability to interact with mammalian and microbial membranes. On the other hand, recent data obtained in both isolated heart and isolated cardiomyocytes suggest that the VS-1 and CSTmediated cardioprotective effects are primarily direct on the myocardium, rather than endothelium-dependent. Anyway, both direct and indirect pathways seem to be characterized by the absence of specific membrane receptors on target cells, highlighting intriguing novelties in the topic of cell signaling, in particular respect to an hypothetical receptor-independent eNOS activation.
Document Type: Research Article
Publication date: 2012-08-01
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.