Insulin potentiates cytokine-induced VCAM-1 expression in human endothelial cells.
Insulin potentiates cytokine-induced VCAM-1 expression in human endothelial cells.
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DOI：
10.1016/j.bbadis.2008.05.006
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发表时间：
2008-09
期刊：
影响因子：
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通讯作者：
R. Madonna;M. Massaro;R. de Caterina
中科院分区：
文献类型：
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作者：
R. Madonna;M. Massaro;R. de Caterina
高胰岛素血症是心血管事件的独立危险因素，可能导致心血管疾病。低级别慢性炎症与动脉粥样硬化的发病机制有关。我们的目的是确定病理生理上高胰岛素浓度对细胞因子诱导的人脐静脉内皮细胞（HUVEC）内皮细胞活化的影响。用胰岛素（0-24 h）±肿瘤坏死因子(TNF)-α或脂多糖（LPS）孵育HUVEC。在病理生理/药理学浓度（10−9-10−7mol/L）下，胰岛素选择性地诱导VCAM-1表达，并增强TNF-α和lps的作用，这种作用被蛋白酶体抑制剂乳酸蛋白酶素逆转。与单独使用TNF-α相比，胰岛素+TNF-α可使U937细胞黏附增加一倍。胰岛素显著增加TNF-α诱导的NF-κB活化，诱导磷酸化的i -κB -α积累。因此，高胰岛素血症增强了细胞因子诱导的内皮细胞中VCAM-1的表达，从而可能导致其他炎症刺激对动脉粥样硬化的有害影响。
Hyperinsulinemia is an independent risk factor for cardiovascular events and may contribute to cardiovascular disease. Low-grade chronic inflammation has been implicated in the pathogenesis of atherosclerosis. We aimed at determining the impact of pathophysiologically high insulin concentrations on cytokine-induced endothelial activation in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with insulin (0–24 h)±tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS). At pathophysiological/pharmacological concentrations (10−9–10−7mol/L), insulin selectively induced VCAM-1 expression and potentiated the effects of TNF-α andLPS, effects reverted by the proteasome inhibitor lactacystin. Compared with TNF-α alone, insulin+TNF-α doubled U937 cell adhesion. Insulin markedly increased TNF-α-induced NF-κB activation and induced phosphorylated IκB-α accumulation. Therefore, hyperinsulinemia enhances cytokine-induced VCAM-1 expression in endothelial cells, thus potentially contributing to detrimental effects of other inflammatory stimuli on atherogenesis.