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The inhibitory effect of alacepril, an angiotensin-converting enzyme inhibitor, on endothelial inflammatory response induced by oxysterol and TNF-α

机译:血管紧张素转换酶抑制剂阿克拉普利对氧固醇和TNF-α诱导的内皮炎性反应的抑制作用

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The objectives were to determine the effects of alacepril, an angiotensin-converting enzyme inhibitor, on the expression of adhesion molecules and monocyte adherence to endothelial cells induced by 7-ketocholesterol (7-KC) and tumor necrosis factor (TNF)-α. We used human aortic endothelial cells (HAECs) and U937 monocytic cells. Surface expression and mRNA levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were determined by EIA and RT-PCR. Adherence of U937 to HAECs was assessed by adhesion assay. Incubation of HAEC with 7-KC increased the surface expression of protein and mRNA levels of ICAM-1 and VCAM-1 on HAECs and the production of reactive oxygen species (ROS) in HAECs. Pretreatment with alacepril reduced the enhanced expression of these molecules in a dose-dependent manner. The inhibitory effect of alacepril against 7-KC or TNF-α-induced CAMs expression was stronger than that of captopril or enalapril. Alacepril inhibited the production of ROS in HAECs stimulated by 7-KC or TNF-α. These results suggest that alacepril works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with monocytes induced by 7-KC and TNF-α.
机译:目的是确定alacepril(一种血管紧张素转化酶抑制剂)对7-酮胆固醇(7-KC)和肿瘤坏死因子(TNF)-α诱导的粘附分子表达和单核细胞粘附于内皮细胞的作用。我们使用了人主动脉内皮细胞(HAEC)和U937单核细胞。通过EIA和RT-PCR测定细胞间粘附分子1(ICAM-1)和血管细胞粘附分子1(VCAM-1)的表面表达和mRNA水平。 U937对HAEC的粘附力通过粘附测定法进行评估。用7-KC孵育HAEC可增加HAEC上ICAM-1和VCAM-1的蛋白质表面表达和mRNA水平,以及HAEC中活性氧的产生。用alacepril预处理以剂量依赖的方式降低了这些分子的增强表达。阿拉克普利对7-KC或TNF-α诱导的CAMs表达的抑制作用强于卡托普利或依那普利。 Alacepril抑制7-KC或TNF-α刺激的HAEC中ROS的产生。这些结果表明,alacepril通过抑制内皮依赖性与7-KC和TNF-α诱导的单核细胞的黏附相互作用而作为抗动脉粥样硬化剂。

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