Effect of simvastatin on monocyte adhesion molecule expression in patientswith hypercholesterolemia

Increased monocyte adherence to the vessel wall is one of the earliest even ts in atherosclerosis. The mechanism by which hypercholesterolemia causes a lterations in endothelial adhesiveness for monocytes is unclear. This study sought to determine if monocyte adhesion molecule expression is affected b y low-density lipoprotein (LDL)-cholesterol levels. Patients with hyperchol esterolemia and stable coronary artery disease were compared with those wit hout major cardiovascular risk (control). Patients with hypercholesterolemi a were treated with simvastatin 20-40 mg/day for 8-10 weeks. Blood samples were examined with flow cytometry assays at baseline and after cholesterol- lowering therapy. Monocyte CD11b and CD14 adhesion molecule expression, mea sured as fluorescence intensity, were significantly (P < 0.0001) higher in hypercholesterolemic patients before the study (176.9 +/- 9.8 and 138.0 +/- 4.8, respectively) when compared with that in control subjects (97.2 +/- 8 .1 and 84.0 +/- 6.4, respectively). Both decreased markedly with treatment: to 118.8 +/- 6.9 and 103.1 +/- 3.9, respectively. Monocyte L-selectin expr ession was significantly lower in patients with hypercholesterolemia before treatment (43.0 +/- 3.0) when compared with control subjects (79.9 +/- 2.7 ), and it increased markedly with treatment (54.2 +/- 2.5). LDL levels corr elated directly with both CD11b and CD14 expression and correlated inversel y with L-selectin expression. These data show that hypercholesterolemia aff ects monocyte adhesion molecule expression which, in turn, decreases with s tatin-induced plasmatic cholesterol reduction. Such perturbations in monocy te function likely represent a proinflammatory response to hypercholesterol emia and may have a role in the early progression of atherogenesis. (C) 200 1 Elsevier Science Ireland Ltd. All rights reserved.