title: Effects of statins on endothelium and endothelial progenitor cell recruitment.
abstract: Statins appear to be potent drugs with a variety of pleiotropic effects with vasculoprotective and cardioprotective activity. The beneficial effects of statins on endothelial cells as well as on endothelial cell function appear to be related to improved nitric oxide bioavailability. Mechanistically, statins induce endothelial nitric oxide synthase mRNA stability in endothelial cells and promote endothelial nitric oxide synthase activity through a PI3K/Akt dependent pathway, which is a common signal transduction pathway shared by growth factors such as vascular endothelial growth factors or fibroblast growth factors (FGFs), estrogens, or statins. Furthermore, statins have potent antiinflammatory capacities by potently interfering with the generation of reactive oxygen species or activating scavenging systems for free radicals such as the thioredoxin system. These mechanisms might all contribute to improved NO bioavailability and confer the beneficial actions of statins. The proangiogenic properties of statins and their effects on reendothelialization following vessel injury include novel actions such as the mobilization, differentiation, and improved survival of endothelial progenitor cells. Statin therapy might reverse the impaired functional regeneration capacities seen in patients with risk factors for coronary artery disease or documented active coronary artery disease by specifically interacting with progenitor cell function. Accordingly, augmentation of functionally active endothelial progenitor cells with improved homing capacity will be a critical step in advancing therapeutic neovascularization as well as reendothelialization in patients with coronary artery disease.
authors.affiliation: Department of Internal Medicine IV, Division of Cardiology and Molecular Cardiology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Walter
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase