PDF(Pubmed)
Abstract：
Endothelial dysfunction plays a key role in the development of liver cirrhosis. Among the biomarkers of endothelial dysfunction, the soluble form of Vascular Adhesion Protein-1 (sVAP-1) is an unconventional and less known adhesion molecule endowed also with amine oxidase activity. The aim of this study was to explore and correlate the behavior of sVAP-1 with that of the soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) and with the severity of liver cirrhosis. A cross-sectional study was carried out by enrolling 28 controls, 59 cirrhotic patients without hepatocellular carcinoma, and 56 patients with hepatocellular carcinoma (HCC), mainly caused by alcohol abuse. The levels of adhesion molecules and of the pro-inflammatory cytokines (IL-6 and TNF-αα) were determined by immunoassay and the enzymatic activity of sVAP-1 by a fluorometric assay. In non-diabetic patients without HCC, a specific behavior of sVAP-1 was highlighted. Differently from sVCAM-1, sICAM-1, and cytokines, the sVAP-1 level was significantly increased only in the early stage of disease, and then, it decreased in the last stage (866 ± 390 ng/mL vs. 545 ± 316 ng/mL, in Child-Pugh class A vs. C, respectively, p < 0.05). Bivariate analysis correlates sVAP-1 to sVCAM-1, in the absence of HCC (Spearman\'s rho = 0.403, p < 0.01). Multiple linear regression analysis revealed that sVCAM-1 appears to be a predictor of sVAP-1 (β coefficient = 0.374, p = 0.021). In conclusion, in non-diabetic and non-HCC cirrhotic patients, sVAP-1 may be a potential prognostic biomarker that, together with sVCAM-1 and pro-inflammatory cytokines, may provide information on the progression of sinusoidal liver endothelium damage.
摘要：
内皮功能障碍在肝硬化的发生发展中起着关键作用。在内皮功能障碍的生物标志物中，血管粘附蛋白-1（sVAP-1）的可溶形式是一种非常规且鲜为人知的粘附分子，也具有胺氧化酶活性。这项研究的目的是探讨sVAP-1的行为与可溶性血管细胞粘附分子-1（sVCAM-1）和细胞间粘附分子-1（sICAM-1）的行为以及与肝硬化的严重程度。通过招募28名对照进行了横断面研究，59例肝硬化患者无肝细胞癌，和56例肝细胞癌（HCC），主要由酗酒引起。通过免疫测定法确定粘附分子和促炎细胞因子（IL-6和TNF-α）的水平，并通过荧光测定法确定sVAP-1的酶活性。在没有HCC的非糖尿病患者中，突出显示了sVAP-1的特定行为。与sVCAM-1、sICAM-1和细胞因子不同，sVAP-1水平仅在疾病早期才显著增加，然后,它在最后阶段降低（866±390ng/mL与545±316纳克/毫升，在Child-PughA级与C,分别,p<0.05)。在没有HCC的情况下，双变量分析将sVAP-1与sVCAM-1相关联（Spearman的rho=0.403，p<0.01）。多元线性回归分析显示sVCAM-1似乎是sVAP-1的预测因子(β系数=0.374,p=0.021)。总之,在非糖尿病和非肝癌肝硬化患者中，sVAP-1可能是一种潜在的预后生物标志物，与sVCAM-1和促炎细胞因子一起，可以提供有关肝窦内皮损伤进展的信息。
