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Plasma soluble adhesion molecules and endothelium-dependent vasodilation in early human atherosclerosis
1Department of Medicine IV, University of Erlangen-Nürnberg, Klinikum Nürnberg-Süd, Breslauerstr. 201, 90471 Nürnberg, Germany.
Insights
Soluble adhesion molecules do not indicate early atherosclerosis in hypercholesterolaemia. These markers of endothelial inflammation are not elevated and do not correlate with impaired vasodilation in patients with high LDL-cholesterol.
Area of Science:
- Cardiovascular Research
- Biomarker Discovery
- Endothelial Function
Background:
- Soluble adhesion molecules (sVCAM-1, ICAM-1, E-selectin) are implicated in atherosclerosis and endothelial activation.
- Impaired endothelium-dependent vasodilation is an early indicator of atherosclerosis.
- The relationship between soluble adhesion molecules and vasodilation in hypercholesterolaemia requires further investigation.
Purpose of the Study:
- To investigate if soluble adhesion molecules are elevated and related to impaired endothelium-dependent vasodilation in hypercholesterolaemic patients.
- To assess the potential of soluble adhesion molecules as early markers for atherosclerosis in this population.
Main Methods:
- Compared 52 hypercholesterolaemic patients (LDL-C 4.89+/-1.26 mmol/l) with 43 healthy controls (LDL-C 2.44+/-0.79 mmol/l).
- Assessed forearm endothelium-dependent vasodilation using intra-arterial acetylcholine infusion and venous occlusion plethysmography.
- Measured plasma concentrations of soluble intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin via ELISA.
Main Results:
- Hypercholesterolaemic patients exhibited significantly impaired endothelium-dependent vasodilation compared to controls (P=0.002).
- Plasma levels of ICAM-1, VCAM-1, and E-selectin were not significantly different between hypercholesterolaemic patients and controls.
- Soluble adhesion molecule levels did not correlate with the degree of endothelium-dependent vasodilation.
Conclusions:
- In hypercholesterolaemic patients without clinical atherosclerosis, soluble adhesion molecule levels are not elevated compared to healthy individuals.
- These markers of endothelial inflammation are not associated with impaired endothelium-dependent vasodilation in this cohort.
- Measurement of soluble adhesion molecules is not a substitute for assessing endothelium-dependent vasodilation in detecting early hypercholesterolaemic atherosclerosis.
Abstract:
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 microg/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 microg/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.