Native LDL-Cholesterol Mediated Monocyte Adhesion Molecule Overexpression is Blocked by Simvastatin
- 87 Downloads
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.
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.
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.
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.
Key wordsNative LDL-cholesterol Adhesion molecules Monocyte Simvastatin Atherosclerosis Inflammation
- 10.Pritchard KA Jr, Tota RR, Lin JH, Danishefsky KJ, Kurilla BA, Holland JA, Stemerman MB. Native low density lipoprotein: endothelial cell recruitment of mononuclear cells. Arterioscler Thromb Vasc Biol 1991;11:1175–81.Google Scholar
- 18.Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation 2004;109:39–43.Google Scholar
- 23.O’Byrne D, Devaraj S, Islam KN, Collazo R, McDonald L, Grundy S, Jialal I. Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal failure patients on dialysis therapy. Metabolism 2001;50:207–15.PubMedCrossRefGoogle Scholar
- 24.SAS Institute Inc.. SAS Procedures Guide for Personal Computers. Version 6 ed.. Cary, NC: SAS Institute Inc.; 1985.Google Scholar
- 27.Navab MSS, Ines SY, Hama GP, Hough LA, Ross R, Bork W, Valente AJ, Berliner JA, Drinkwater DC, Laks H, Fogelman AM. Monocyte transmigration induced by modification of low density lipoprotein in coculture of human aortic wall cells is due to induction of MCP-1 and abolished by high density lipoprotein. J Clin Invest 1991;88:2039–46.PubMedCrossRefGoogle Scholar