Comparison of the Efficacies of Five Different Statins on Inhibition of Human Saphenous Vein Smooth Muscle Cell Proliferation and Invasion
- 1 October 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Cardiovascular Pharmacology
- Vol. 50 (4), 458-461
- https://doi.org/10.1097/fjc.0b013e318123767f
Abstract
Statins (HMG-CoA reductase inhibitors) exhibit beneficial effects on the vasculature independently of their cholesterol-lowering properties. These pleiotropic effects underlie the ability of statins to reduce intimal hyperplasia in saphenous vein (SV) bypass grafts by attenuating smooth muscle cell (SMC) invasion and proliferation. Although all statins can effectively lower cholesterol, the pleiotropic effects of individual statins may well differ. We therefore compared the concentration-dependent effects of 4 lipophilic statins (simvastatin, atorvastatin, fluvastatin, and lovastatin) and 1 hydrophilic statin (pravastatin) on the proliferation and invasion of SMC cultured from SV of 9 different patients undergoing coronary artery bypass grafting (CABG). The lipophilic statins inhibited SV-SMC proliferation over a 4-day period with an order of potency of fluvastatin > atorvastatin > simvastatin > lovastatin (IC50 range = 0.07 to 1.77 microM). Similarly, these statins also inhibited SV-SMC invasion through an artificial basement membrane barrier (fluvastatin > atorvastatin > simvastatin >> lovastatin; IC50 range = 0.92 to 26.9 microM). In contrast, the hydrophilic pravastatin had no significant effect on SV-SMC proliferation at concentrations up to 10 microM, nor did it attenuate SV-SMC invasion (up to 30 microM). Our data provide strong evidence that individual statins possess differential pleiotropic effects on SV-SMC function. This may be of clinical relevance in the selection of individual statins for the treatment of CABG patients.Keywords
This publication has 26 references indexed in Scilit:
- Hydrophilic statin suppresses vein graft intimal hyperplasia via endothelial cell-tropic Rho-kinase inhibitionJournal of Vascular Surgery, 2005
- PLEIOTROPIC EFFECTS OF STATINSAnnual Review of Pharmacology and Toxicology, 2005
- Rho-Kinase Is an Important Therapeutic Target in Cardiovascular MedicineArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Simvastatin inhibits MMP‐9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP‐9 mRNA levelsThe FASEB Journal, 2005
- Unravelling Ras signals in cardiovascular disease.Nature, 2004
- Role of statin therapy in the coronary bypass patientThe Annals of Thoracic Surgery, 2004
- Statins in coronary bypass surgery: rationale and clinical useThe Annals of Thoracic Surgery, 2003
- Preoperative lipid control with simvastatin protects coronary artery bypass grafts from obstructive graft diseaseThe American Journal of Cardiology, 2001
- Preoperative lipid control with simvastatin reduces the risk for graft failure already 1 year after myocardial revascularizationCardiovascular Surgery, 2000
- 3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitors Attenuate Vascular Smooth Muscle Proliferation by Preventing Rho GTPase-induced Down-regulation of p27Published by Elsevier BV ,1999