Angiotensin-converting enzyme inhibitors (ACEIs) provide clinical benefit in patients suffering from cardiac failure, acute myocardial infarction, and diabetes complications through actions on dysfunctional endothelium. Protection of the endothelium by ACEIs has been attributed to regulation of endothelial nitric-oxide synthase (eNOS), engagement of its downstream effectors, and up-regulation of fibroblast growth factor-2 (FGF-2), providing the coronary endothelium with a survival advantage. In this issue, Donnini et al. further detail the mechanisms by which ACEIs, particularly sulfhydryl (SH) containing ACEIs such as zofenoprilat, impart a survival benefit for endothelial cells. These ACEIs activate the phosphatidylinositol 3-kinase/Akt survival pathway and eNOS signaling that promotes mitogen-activated protein kinase activation and the expression of FGF-2 and telomerase reverse transcriptase, ultimately, providing endothelial cell protection against apoptosis and replicative senescence. These observations with SH containing ACEIs suggest that these drugs could provide a clinical benefit in cardiovascular disease through protection against endothelial damage and premature vascular aging.
See article at J Pharmacol Exp Ther 2010, 332:776–784.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics