Novel modulator for endothelial adhesion molecules - Adipocyte-derived plasma protein adiponectin
Novel modulator for endothelial adhesion molecules - Adipocyte-derived plasma protein adiponectin
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DOI：
10.1161/01.cir.100.25.2473
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发表时间：
1999-12-21
期刊：
影响因子：
37.8
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Ouchi, N;Kihara, S;Matsuzawa, Y
背景-在众多的脂肪细胞源性内分泌因子中，我们最近发现了一种脂肪细胞特异性分泌蛋白脂联素，它在肥胖时减少。虽然肥胖与心血管疾病的发病率和死亡率增加有关，但肥胖与血管疾病之间联系的分子基础尚未完全阐明。本研究探讨是否脂联素可以调节内皮功能和冠状动脉diseases.Methods和结果在体外研究中，人主动脉内皮细胞（HAECs）预孵育18小时，指定量的脂联素，然后暴露于肿瘤坏死因子-α（TNF-α）（10 U/mL）或车辆的时间指示。粘附实验检测人单核细胞系THP-1细胞与HAECs的粘附。采用细胞ELISA法检测血管细胞粘附分子1（VCAM-1）、内皮细胞-白细胞粘附分子1（E-selectin）和细胞内粘附分子1（ICAM-1）的表面表达。生理浓度的脂联素剂量依赖性地抑制TNF-α诱导的THP-1粘附和HAECs上VCAM-1、E-选择素和ICAM-1的表达。在体内研究中，通过我们最近开发的夹心ELISA系统测定人血浆中脂联素的浓度。血浆脂联素浓度显着降低冠心病患者比那些在年龄和体重指数调整的对照subjects. Conclusions，这些观察结果表明，脂联素调节内皮炎症反应和血浆脂联素水平的测量可能有助于评估CAD的风险。
Background-Among the many adipocyte-derived endocrine factors, we recently found an adipocyte-specific secretory protein, adiponectin, which was decreased in obesity. Although obesity is associated with increased cardiovascular mortality and morbidity, the molecular basis for the link between obesity and vascular disease has not been fully clarified. The present study investigated whether adiponectin could modulate endothelial function and relate to coronary disease.Methods and Results-For the in vitro study, human aortic endothelial cells (HAECs) were preincubated for 18 hours with the indicated amount of adiponectin, then exposed to tumor necrosis factor-alpha (TNF-alpha) (10 U/mL) or vehicle for the times indicated. The adhesion of human monocytic cell line THP-1 cells to HAECs was determined by adhesion assay. The surface expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intracellular adhesion molecule-1 (ICAM-1) was measured by cell ELISA. Physiological concentrations of adiponectin dose-dependently inhibited TNF-alpha-induced THP-1 adhesion and expression of VCAM-1, E-selectin, and ICAM-1 on HAECs. For the in vivo study, the concentrations of adiponectin in human plasma were determined by a sandwich ELISA system that we recently developed. Plasma adiponectin concentrations were significantly lower in patients with coronary artery disease than those in age- and body mass index-adjusted control subjects.Conclusions-These observations suggest that adiponectin modulates endothelial inflammatory response and that the measurement of plasma adiponectin levels may be helpful in assessment of CAD risk.