Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia.

High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule [ICAM-1], E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 ± 10 years, waist/hip circumference ratio 0.89 ± 0.07, LDL-cholesterol [LDL-c] 4.9 ± 1.3 mmol/L, triglycerides 1.8 ± 0.9 mmol/L, HDL-c 1.3 ± 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v ≥ 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P < .05), higher triglycerides (P < .001), higher body mass index (P < .02), lower FMV (3.7% ± 2.0% v 4.9% ± 3.4%, P < .002), higher VCAM-1 (1,195 ± 395 ng/mL v 984 ± 303 ng/mL, P < .01), and higher ICAM-1 (406 ± 78 ng/mL v 364 ± 68 ng/mL, P < .01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P = .003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P < .05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules.