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Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis
R De Caterina1, G Basta, G Lazzerini
1CNR Institute of Clinical Physiology, University of Pisa, Italy. rdecater@po.ifc.pi.cnr.it
Insights
Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a strong indicator of atherosclerosis severity. This biomarker is independently associated with intima-media thickness, suggesting its role in endothelial activation.
Area of Science:
- Cardiovascular Biology
- Biomarkers
- Atherosclerosis Research
Background:
- Vascular cell adhesion molecule-1 (VCAM-1) is expressed on activated endothelial cells and implicated in early atherosclerosis.
- Soluble VCAM-1 (sVCAM-1) is detectable in plasma, suggesting its potential as a circulating marker.
Purpose of the Study:
- To investigate if sVCAM-1 is a circulating marker for the presence and severity of human atherosclerosis.
- To compare sVCAM-1 with other adhesion molecules and markers of endothelial dysfunction in relation to atherosclerosis.
Main Methods:
- Compared plasma sVCAM-1 levels in patients with hypertension and peripheral vascular disease (PVD), uncomplicated hypertension (UH), and healthy controls.
- Assessed plasma concentrations of sVCAM-1, sE-selectin, sICAM-1, s-thrombomodulin, PAI-I, vWF, insulin, glucose, fibrinogen, lipids, and urinary albumin excretion (UAE).
- Correlated biomarker levels with carotid intima-media thickness (IMTmax) via echography.
Main Results:
- PVD patients exhibited significantly higher IMTmax and plasma sVCAM-1 levels compared to UH patients and controls.
- sVCAM-1 levels were higher in PVD patients (990 ng/mL) than in UH (340 ng/mL) and controls (386 ng/mL).
- sVCAM-1 was the strongest correlate of IMTmax (R = .59, P < .001) and remained the sole independent predictor in multivariate analysis.
Conclusions:
- sVCAM-1 is a significant biohumoral correlate of overt atherosclerosis, independent of hypertension.
- sVCAM-1 may serve as an in vivo marker of endothelial activation.
- Further research is needed to determine the value of sVCAM-1 in global risk assessment and intervention studies.
Abstract:
Vascular cell adhesion molecule-1 (VCAM-1) is a protein expressed on the surface of activated endothelial cells and expressed in early atherosclerosis. Because part of the protein is shed in the circulation and can be detected in peripheral plasma [soluble (s) VCAM-1], we hypothesized that sVCAM-1 may be a circulating marker of the presence and severity of atherosclerosis in humans. We selected 11 patients with essential hypertension plus peripheral vascular disease (PVD) and matched them for age, gender, body mass index, and smoking habits with 11 patients with uncomplicated essential hypertension (UH) and 11 healthy controls. We evaluated plasma concentrations of sVCAM-1 along with those of the soluble form of two other endothelial leukocyte adhesion molecules [sE-selectin and s-intercellular adhesion molecule-1 (sICAM-1)] and other markers of endothelial dysfunction/ damage [s-thrombomodulin, plasminogen activator inhibitor type I, and von Willebrand factor (vWF)]. We also measured insulin, glucose, fibrinogen, total and HDL cholesterol, and the urinary albumin excretion (UAE), which may also be related to atherosclerosis. Results of these assays were related to the echographic assessment of the maximum intima-media thickness (IMTmax) at the carotid bifurcation, as an index of atherosclerosis in the carotids. PVD patients had a clearly elevated IMTmax [2.7 (1.1-3.1) mm, median (range)] compared with both UH patients [1.2 (0.8-2.4) mm] and controls [1 (0.6-2) mm]. sVCAM-1 was clearly higher in PVD patients [990 (273-1808) ng/mL, median (range)] versus 340 (236-975) ng/mL in UH and 386 (204-835) ng/mL in controls, and it separated clinical categories better than sICAM-1, vWF, glucose, insulin, UAE, triglycerides, or total, LDL or HDL cholesterol, sVCAM-1 was also the best biohumoral correlate of IMTmax (R = .59; P < .001) in univariate analysis. Because many of the biohumoral variables assessed were mutually intercorrelated, they were entered in a multivariate analysis to assess their contribution in explaining IMTmax variability. sVCAM-1 remained the only independent predictor of IMTmax and totally abolished the contribution of other variables to IMTmax variability. Thus, sVCAM-1 is a good biohumoral correlate of overt atherosclerosis, independent of underlying hypertension, and may be an in vivo marker of endothelial activation. Its potential value as a surrogate for global risk assessment and its behavior in intervention studies remain to be determined.