Plasma soluble adhesion molecules and endothelium-dependent vasodilation in early human atherosclerosis

Levels of soluble cellular adhesion molecules are increased in patients with atherosclerosis, and have been found to predict coronary heart disease. Therefore these molecules have been suggested to represent laboratory markers for inflammation and activation of endothelial cells. Impaired endothelium-dependent vasodilation has been demonstrated to be an early marker of atherosclerosis. We hypothesized that soluble adhesion molecules are related to impaired endothelium-dependent vasodilation and may serve as an early marker of atherosclerosis. Patients (n = 52) with moderate and uncomplicated hypercholesterolaemia [low-density lipoprotein (LDL)-cholesterol 4.89±1.26 mmol/l] were compared with healthy controls (n = 43; LDL-cholesterol 2.44±0.79 mmol/l). Endothelium-dependent vasodilation of the forearm vasculature was assessed by intra-arterial infusion of acetylcholine (12 and 48 µg/min). Forearm blood flow was measured by venous occlusion plethysmography. Plasma concentrations of the soluble forms of ICAM-1 (intercellular cell adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and E-selectin were measured by ELISA. Hypercholesterolaemic patients had impaired endothelium-dependent vasodilation in comparison with healthy controls (forearm blood flow after 48 µg/min acetylcholine: 21.3±10.6 and 30.4±16.3 ml·min^-1·100 ml^-1 respectively; P = 0.002). Plasma concentrations of soluble adhesion molecules were not different between hypercholesterolaemic patients and controls (ICAM-1, 196±56 and 180±38 ng/ml respectively; VCAM-1, 431±137 and 405±65 ng/ml respectively; E-selectin, 39±17 and 37±12 ng/ml respectively). Moreover, levels of soluble adhesion molecules were not correlated with endothelium-dependent vasodilation. Thus, in hypercholesterolaemic patients without clinical atherosclerosis, levels of soluble adhesion molecules were not elevated in comparison with healthy controls. In addition, these markers of endothelial inflammation were not related to impaired endothelium-dependent vasodilation. Our data indicate that measurement of levels of soluble adhesion molecules cannot replace assessment of endothelium-dependent vasodilation in detection of early hypercholesterolaemic atherosclerosis.