Simvastatin Reduces the Expression of Adhesion Molecules in Circulating Monocytes From Hypercholesterolemic Patients

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Abstract
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)... Statins are able to reduce the rate of cardiovascular disease in a pathway independent of cholesterol lowering. We demonstrated that treatment with simvastatin reduced the expression of cellular adhesion molecules (ICAM-1 and LFA-1) in monocytes in vivo and in vitro. Three statins tested in vitro reduced the expression/production of these cellular adhesion molecules by human umbilical vein endothelial cells.