title: Simvastatin enhances the regeneration of endothelial cells via VEGF secretion in injured arteries.
abstract: The search for a novel therapy for endothelial regenerating is an area of intensive investigation. Recent experimental and clinical evidence strongly suggests that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have several physiological effects independent of low-density lipoprotein cholesterol reduction. We here report that the carotid arterial blood flow after endothelial injury in hamsters treated with simvastatin was restored, in contrast to the situation in nontreated hamsters. Histologic observations showed a prompt recovery of endothelial cells with a much higher DNA synthesis index in repaired endothelium of hamsters treated with simvastatin. The amount of secreted vascular endothelial cell growth factor (VEGF) by cultured vascular smooth muscle cells from hamsters treated with simvastatin was significantly increased. Mevalonate reduced the amount of VEGF secretion by simvastatin in vitro. Finally, an injection of either an anti-VEGF antibody or an anti-VEGF receptor-1 (Flt-1) antibody, but not anti-VEGF receptor-2 (Flk-1), reduced the prompt endothelial healing. Simvastatin regulates endothelial regenerating by an over-release of VEGF and by this may result in prompt endothelial healing after vascular injury. Our results provide new insights into the role of statin and VEGF in the pathogenesis of vascular diseases.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Gifu, Japan. leuven@cc.gifu-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuno
authors.forename: Mariko
authors.initials: M
authors.lastname: Takei
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hayashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Ishisaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008798:Mevalonic Acid / Q000494:pharmacology; D012039:Regional Blood Flow; D019821:Simvastatin / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000502:physiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D019821:Simvastatin; D008798:Mevalonic Acid