Circulating Vascular Cell Adhesion Molecule-1 Correlates With the Extent of Human Atherosclerosis in Contrast to Circulating Intercellular Adhesion Molecule-1, E-Selectin, P-Selectin, and Thrombomodulin

Abstract

Secondary prevention of atherosclerosis, especially before the onset of symptoms, appears desirable and could be possible with a serum marker detecting atherosclerosis. Circulating, shedded forms of adhesion molecules may serve as such because their expression is upregulated in atherosclerotic plaques. In 52 patients with peripheral arterial vascular disease (Fontaine class IIa, 7 patients; class IIb, 29 patients; and class III, 16 patients), the extent of atherosclerosis was evaluated on the basis of angiograms of a large portion of the arterial system. The area diseased by atherosclerosis was determined by the percentage of vessel wall irregularities of the following calculated segments: aorta (distal from the kidney arteries), common iliac artery, external iliac artery, common femoral artery, lateral circumflex femoral artery, and popliteal artery. The maximal surface area that could exhibit atherosclerotic changes was 250 cm2. The serum concentration of circulating vascular cell adhesion molecule-1 (VCAM-1) correlated with the extent of atherosclerosis (r = .8, P < .001). In contrast, circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin (as markers for endothelial cell damage) did not correlate with the extent of atherosclerosis. Furthermore, circulating VCAM-1 could be used to indicate stages of atherosclerosis with a high degree of statistical significance. The potential bias of factors such as age, diabetes mellitus, hypercholesterolemia, arterial hypertension, renal failure, and history of myocardial infarction on the correlation of circulating VCAM-1 with the extent of atherosclerosis could be excluded by multivariate analysis. These findings suggest an important role of VCAM-1 in atherosclerosis and may serve as the basis for further evaluation of circulating VCAM-1 as a potential serum marker for atherosclerosis.

Soluble Cell Adhesion Molecules in Hypertriglyceridemia and Potential Significance on Monocyte Adhesion

“…As previously mentioned, it is unlikely that fish oil therapy for Ͻ1 year significantly changed the extent of atherosclerosis, which has been shown to correlate to the levels of VCAM-1 in one study. 34 In this study, we found that the levels of sE-selectin were increased after administration of n-3 fatty acids for 6 weeks and then decreased after more prolonged treatment. Although the mechanisms by which these soluble molecules are released into the circulation are not well known, Newman et al 35 demonstrated that membrane-bound E-selectin was cleaved into the soluble form in vitro.…”

“…33 However, it is highly improbable that treatment of dyslipidemia with fish oils could lead to a significant reduction in the extent of atherosclerosis within 12 months based on previous clinical data. 34 In our previous study, levels of sE-selectin but not sICAM-1 were significantly decreased after treatment of hypercholesterolemia with an HMG-CoA reductase inhibitor for 6 months.…”

Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release

“…Thus, other mechanisms must be active in non-insulin-dependent diabetic patients without complications and these lead to earliest endothelial changes. In this context, circulating concentrations of soluble VCAM-1 but not of other endothelial adhesion molecules, i. e. intercellular adhesion molecule-1, E-selectin and P-selectin and thrombomodulin correlated with the extent and severity of atherosclerosis in humans [10]. …”

Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light?

“…27,34 There are, however, some notable exceptions. 31,35 Soluble ICAM-1, soluble VCAM-1 and atherogenic risk factors Although the available evidence does suggest a relation between sICAM-1, sVCAM-1 and atherosclerosis, the extent of the association is debated and it remains uncertain whether they are independent indicators. 22,36 As Rizzoni and colleagues report, many risk factors for atherosclerosis, including diabetes and hypertension, are generally (though not always) associated with increased levels of sICAM-1 and sVCAM-1.…”