Published online before print January 30, 2003, doi: 10.1161/01.ATV.0000059384.34874.F0
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© 2003 American Heart Association, Inc.
Vascular Biology |
Simvastatin Reduces the Expression of Adhesion Molecules in Circulating Monocytes From Hypercholesterolemic Patients
From the Clinic of Internal Medicine II, Department of Angiology (A.R-M., R.A.B., G-H.S., T.M., E.M., M.B.), Department of Vascular Biology and Thrombosis Research (G.W.P., B.R.B.), Department of Anesthesiology and Intensive Care (B) (H-G.K.), and Department of Internal Medicine I (P.V.), Division of Hematology and Hemostaseology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Correspondence to Mehrdad Baghestanian, MD, Associate Professor of Vascular Biology, Department of Internal Medicine II, Division of Angiology, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail Mehrdad.Baghestanian{at}univie.ac.at
Objective— The intercellular adhesion molecule-1 (ICAM-1/CD54) and its ligand, CD11a/CD18, mediate endothelial adhesion of leukocytes and their consecutive transmigration. Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte–endothelial interactions. We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro.
Methods and Results— A total number of 107 hypercholesterolemic patients were treated with 20 mg (n=52) or 40 mg (n=55) of simvastatin daily. After 6 weeks of treatment, peripheral blood mononuclear cells (PBMCs) expressed lower amounts of CD54-, CD18-, and CD11a-mRNA compared with pretreatment values. Surface expression of CD54 and CD18/CD11a on CD14+-monocytes also decreased significantly in both groups of patients. Moreover, simvastatin, atorvastatin, and cerivastatin were found to downregulate tumor necrosis factor (TNF)-
–induced expression of CD54 and CD18/CD11a in isolated PBMCs obtained from normal donors as well as TNF-–dependent expression of these CAMs in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, all three statins were found to reduce the binding of PBMCs to TNF-–stimulated HUVECs in vitro.
Conclusions— Statin-induced inhibition of expression of CD54 and CD18/CD11a in PBMCs and HUVECs with consecutive loss of adhesive function may contribute to the anti-inflammatory effects of these drugs and some of their beneficial clinical activities.
Key Words: atherosclerosis • cholesterol • leukocytes • endothelium • cell adhesion molecules
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