De Caterina R, Basta G, Lazzerini G, Dell'Omo G, Petrucci R, Morale M, Carmassi F, Pedrinelli R
CNR Institute of Clinical Physiology, University of Pisa, Italy.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2646-54. doi: 10.1161/01.atv.17.11.2646.
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.
血管细胞黏附分子-1（VCAM-1）是一种在活化内皮细胞表面表达的蛋白质，在动脉粥样硬化早期也有表达。由于该蛋白的一部分会释放入循环系统，并可在外周血浆中检测到[可溶性（s）VCAM-1]，我们推测sVCAM-1可能是人类动脉粥样硬化存在及严重程度的循环标志物。我们选取了11例原发性高血压合并周围血管疾病（PVD）患者，并将其与11例单纯原发性高血压（UH）患者及11名健康对照者按年龄、性别、体重指数和吸烟习惯进行匹配。我们评估了sVCAM-1以及另外两种内皮白细胞黏附分子的可溶性形式[可溶性E选择素和可溶性细胞间黏附分子-1（sICAM-1）]的血浆浓度，以及内皮功能障碍/损伤的其他标志物[可溶性血栓调节蛋白、纤溶酶原激活物抑制剂I型和血管性血友病因子（vWF）]。我们还测量了胰岛素、葡萄糖、纤维蛋白原、总胆固醇和高密度脂蛋白胆固醇，以及尿白蛋白排泄量（UAE），这些指标也可能与动脉粥样硬化有关。这些检测结果与颈动脉分叉处最大内膜中层厚度（IMTmax）的超声评估结果相关，IMTmax作为颈动脉粥样硬化的一个指标。与UH患者[1.2（0.8 - 2.4）mm]和对照组[1（0.6 -2）mm]相比，PVD患者的IMTmax明显升高[2.7（1.1 - 3.1）mm，中位数（范围）]。PVD患者的sVCAM-1明显高于UH患者[340（236 - 975）ng/mL]和对照组[386（204 - 835）ng/mL]，分别为[990（273 - 1808）ng/mL，中位数（范围）]，并且它比sICAM-1、vWF、葡萄糖、胰岛素、UAE、甘油三酯或总胆固醇、低密度脂蛋白或高密度脂蛋白胆固醇能更好地区分临床类别。在单变量分析中，sVCAM-1也是IMTmax的最佳生物体液相关指标（R = 0.59；P < 0.001）。由于所评估的许多生物体液变量相互关联，因此将它们纳入多变量分析以评估它们在解释IMTmax变异性方面的作用。sVCAM-1仍然是IMTmax的唯一独立预测因子，并且完全消除了其他变量对IMTmax变异性的影响。因此，sVCAM-1是明显动脉粥样硬化的良好生物体液相关指标，独立于潜在的高血压，并且可能是内皮激活的体内标志物。其作为全球风险评估替代指标的潜在价值及其在干预研究中的表现仍有待确定。
