Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin

Aim of the study: This study sought to evaluate the effect of nLDL concentrations on monocyte adhesion molecule expression in hypercholesterolemic patients with stable coronary artery disease (CAD) and to determine whether lipid-lowering therapy with simvastatin would change this effect. Methods: Blood samples from patients with hypercholesterolemia (mean LDL 152 mg/dL) and CAD (HC, n∈=∈23) were collected before and after a 12-week treatment with 40 mg of simvastatin. Healthy individuals (mean LDL 111 mg/dL) were used as controls (CT, n∈=∈15). Isolated nLDL, at a fixed concentration of 100 mg/dL, was added to monocyte suspensions obtained before and after the simvastatin treatment. Monocyte activation was determined by changes in cellular adhesion molecule expression. Results: In response to nLDL, CD11b and CD14 adhesion molecule expression was higher in HC patients than in CT patients before treatment (174.2∈±∈8.4 vs 102.2∈±∈6.3, P∈<∈0.03 and 140.4∈±∈5.0 vs 90. 4∈±∈6.7, P∈<∈0.04). After simvastatin treatment, CD11b expression decreased to 116.9∈±∈12.5 (P∈<∈0. 03) and CD14 expression to 107.5∈±∈6.2 (P∈<∈0.04). Alternatively, L-selectin expression was lower in HC patients than in CT patients before therapy (46.0∈±∈3.5 vs 62. 1∈±∈5.5, P∈<∈0.04), and it increased markedly after lipid reduction to 58.7∈±∈5.0 (P∈<∈0.04 vs baseline). After simvastatin treatment, LDL was reduced to mean 101.5 mg/dL. Conclusions: These data demonstrate that monocytes from HC patients are more prone to marked nLDL-mediated changes of adhesion molecule expression than monocytes from controls. Simvastatin is capable of inhibiting such nLDL effects. This proinflammatory response to nLDL may have a role in the early onset of atherosclerosis.