Molecular mechanism of vasorelaxant and antiatherogenic effects of the statins in the human saphenous vein graft

• Published in: European journal of pharmacology Vol. 666; no. 1; pp. 150 - 157
• Main Authors: Yaktubay Döndaş, Naciye, Sucu, Nehir, Coşkun Yilmaz, Banu, Kaplan, Halil Mahir, Özeren, Murat, Karaca, Mehmet Kerem, Vezir, Özden, Şingirik, Ergin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2011; Elsevier
• Subjects: Angiotensin II - metabolism; Atherosclerosis - drug therapy; Biological and medical sciences; Cardiology. Vascular system; Coronary Artery Bypass; Coronary artery bypass surgery; Coronary heart disease; Female; Heart; Human saphenous vein graft; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; In Vitro Techniques; Male; Medical sciences; Middle Aged; Molecular mechanism; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; rho-Associated Kinases - metabolism; Saphenous Vein - drug effects; Saphenous Vein - metabolism; Saphenous Vein - physiology; Saphenous Vein - transplantation; Statin; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use; Coronary artery bypass surgery; Statin; Human saphenous vein graft; Molecular mechanism; Human; Vasodilator agent; Cardiovascular disease; Statin derivative; Coronary heart disease; Blood vessel; Surgery; Graft; Circulatory system; Mechanism of action; Vein; Antilipemic agent
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.05.013

In this study we aimed to investigate the vasorelaxant and antiatherogenic effects of the statins (fluvastatin and pravastatin) in the human saphenous vein grafts at the molecular level by using histopathologic, pharmacological and immunochemical techniques. The saphenous vein grafts evaluated histopathologically displayed a loss in their endothelium up to a ratio of 30% and set forth indications of functional deterioration. The pharmacological evaluations proved that the relaxation responses induced by fluvastatin and pravastatin were significantly inhibited by nitric oxide synthase inhibitor, N G-nitro- l-arginine, and cyclooxygenase inhibitor, indomethacin, while these responses were significantly increased by angiotensin converting enzyme inhibitors, captopril and enalapril, and rho kinase inhibitor, Y27632. The results of immunochemical studies are in accordance with the results of the pharmacological studies that the related statins increased the levels of nitric oxide, phospholipase A 2 and they decreased the levels of angiotensin II and active rho kinase. On the other hand mevalonolactone, a substrate of lipid metabolism, failed to change the effects of fluvastatin and pravastatin in the related tissue. The experimental results indicate that activation of nitric oxide synthase and phospholipase A 2-cyclooxygenase pathway and inhibition of angiotensin converting enzyme and rho kinase may have a role on the effects of fluvastatin and pravastatin in the human saphenous vein grafts. It seems that the vasorelaxant and antiatherogenic effects of the related statins are independent of their lipid lowering mechanism.