Effect of simvastatin on monocyte adhesion molecule expression in patients with hypercholesterolemia

Increased monocyte adherence to the vessel wall is one of the earliest events in atherosclerosis. The mechanism by which hypercholesterolemia causes alterations in endothelial adhesiveness for monocytes is unclear. This study sought to determine if monocyte adhesion molecule expression is affected by low-density lipoprotein (LDL)-cholesterol levels. Patients with hypercholesterolemia and stable coronary artery disease were compared with those without major cardiovascular risk (control). Patients with hypercholesterolemia 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, measured 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 expression 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 correlated directly with both CD11b and CD14 expression and correlated inversely with L-selectin expression. These data show that hypercholesterolemia affects monocyte adhesion molecule expression which, in turn, decreases with statin-induced plasmatic cholesterol reduction. Such perturbations in monocyte function likely represent a proinflammatory response to hypercholesterolemia and may have a role in the early progression of atherogenesis.