Oxidized cholesteryl linoleates stimulate endothelial cells to bind monocytes via the extracellular signal-regulated kinase 1/2 pathway
Oxidized cholesteryl linoleates stimulate endothelial cells to bind monocytes via the extracellular signal-regulated kinase 1/2 pathway
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DOI：
10.1161/01.atv.0000012782.59850.41
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发表时间：
2002-04-01
影响因子：
8.7
通讯作者：
Leitinger, N
中科院分区：
文献类型：
--
作者：
Huber, J;Boechzelt, H;Leitinger, N
胆固醇酯的氧化产物已被证明存在于氧化的低密度脂蛋白和动脉粥样硬化病变中。单核细胞与内皮细胞的粘附是动脉粥样硬化形成的关键起始事件。在这里，我们表明，在体外氧化胆固醇亚油酸酯（oxCL）刺激人脐静脉内皮细胞（HUVECs）结合人外周血单核细胞以及单核细胞样U937细胞，但不是外周血中性粒细胞，或嗜中性粒细胞样HL-60细胞。在氧化产物中。9-氧代壬酰胆固醇（9-ONC）和胆固醇亚油酸氢过氧化物刺激U937细胞粘附。OxCL诱导的U937细胞粘附被针对纤维连接蛋白连接片段-1区域的抗体抑制。oxCL和9-ONC均不诱导经典核因子-κ B途径的激活。相反，用oxCL刺激HUVECs导致细胞外信号调节激酶1/2磷酸化。此外，9-ONC和oxCL诱导的U937细胞粘附被丝裂原活化蛋白激酶/细胞外信号调节激酶抑制剂和蛋白激酶C抑制剂阻断。总之，oxCL刺激HUVEC特异性结合单核细胞，涉及内皮连接片段-1和蛋白激酶C和促分裂原活化蛋白激酶依赖性途径的活化。就这样。氧化胆固醇酯可能作为新的介质在动脉粥样硬化的发生和发展中发挥重要作用。
Oxidation products of cholesteryl esters have been shown to be present in oxidized low density lipoprotein and in atherosclerotic lesions. Monocyte adhesion to the endothelium is an initiating crucial event in atherogenesis. Here, we show that in vitro oxidized cholesteryl linoleate (oxCL) stimulated human umbilical vein endothelial cells (HUVECs) to bind human peripheral blood mononuclear cells as well as monocyte-like U937 cells but not peripheral blood neutrophil, or neutrophil-like HL-60 cells. Among the oxidation products contained in oxCLs. 9-oxononanoyl cholesterol (9-ONC) and cholesteryl linoleate hydroperoxides stimulated U937 cell adhesion. OxCL-induced U937 cell adhesion was inhibited by an antibody against the connecting segment-1 region of fibronectin. Neither oxCL nor 9-ONC induced activation of the classical nuclear factor-kappaB pathway. In contrast, stimulation of HUVECs with oxCL resulted in phosphorylation of the extracellular signal-regulated kinase 1/2. Moreover, U937 cell adhesion induced by 9-ONC and oxCL was blocked by a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor and a protein kinase C inhibitor. Taken together, oxCLs stimulate HUVECs to specifically bind monocytes, involving endothelial connecting segment-1 and the activation of a protein kinase C- and mitogen-activated protein kinase-dependent pathway. Thus. oxidized cholesteryl esters may play an important role as novel mediators in the initiation and progression of atherosclerosis.