Statins reduce oxidized low-density lipoprotein levels, but do not alter soluble intercellular cell-adhesion molecule-1 and vascular cell-adhesion molecule-1 levels in subjects with hypercholesterolaemia.
ICAM-1 (intercellular cell-adhesion molecule-1) and VCAM-1 (vascular cell-adhesion molecule-1) are cell-adhesion molecules that have an essential role in monocyte recruitment. In the present study we have investigated (i) whether statins reduce soluble levels of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1), and the relationship between resistance of LDL (low-density lipoprotein) to in vitro oxidation and sICAM-1 and sVCAM-1 levels. Whole blood samples were obtained from 55 healthy non-smoking adults (aged 35-65 years) with moderate (LDL-cholesterol, 3.4-4.9 mmol/l) hypercholesterolaemia participating in a randomized double-blinded, 8-week trial comparing pravastatin (40 mg), simvastatin (20 and 80 mg) and placebo. sICAM-1 levels (means+/-S.D.) increased slightly from 12.2+/-4.2 to 13.6+/-4.2 ng/ml with statin therapy, whereas, among placebo-assigned subjects, levels were unchanged (11.8+/-5.0 and 11.8+/-3.9 ng/ml). sVCAM-1 increased from 18.9+/-10.1 to 21.1+/-7.4 ng/ml among those on active therapy and slightly declined with placebo assignment (19.8+/-8.8 to 19.4+/-6.4 ng/ml). Lag times increased with statin therapy from 74.3+/-39.8 min to 98.3+/-57.8 min ( P =0.003), and were unchanged in the placebo group (from 103.1+/-61.1 to 90.8+/-65.9 min; P =0.48). There were no significant changes between statin and placebo therapy for sICAM-1, sVCAM-1 or lag times ( P =0.09, 0.16 and 0.067 respectively). Changes in sICAM-1 and sVCAM-1 were not correlated with the change in lag times. In contrast with the known effects of oxidized LDL on gene activation of ICAM-1 and VCAM-1, lag times did not correlate with sICAM-1 and sVCAM-1. Statin therapy improved lag times, but has no effect on sICAM-1 or sVCAM-1 levels.
Rosenson
Robert S
RS
Preventive Cardiology Center, Northwestern University, The Feinberg School of Medicine, 201 East Huron Street, Galter Pavilion, Chicago, IL 60611, U.S.A. r-rosenson@northwestern.edu
Wolff
David
D
Tangney
Christine C
CC
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin; D017035:Pravastatin