Shimozawa Makoto, Naito Yuji, Manabe Hiroki, Uchiyama Kazuhiko, Katada Kazuhiro, Kuroda Masaaki, Nakabe Nami, Yoshida Norimasa, Yoshikawa Toshikazu
Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Redox Rep. 2004;9(6):354-9. doi: 10.1179/135100004225006876.
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)-alpha. 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-alpha-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-alpha. These results suggest that alacepril works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with monocytes induced by 7-KC and TNF-alpha.
目的是确定血管紧张素转换酶抑制剂阿拉普利对7-酮胆固醇（7-KC）和肿瘤坏死因子（TNF）-α诱导的黏附分子表达以及单核细胞与内皮细胞黏附的影响。我们使用了人主动脉内皮细胞（HAECs）和U937单核细胞。通过酶免疫分析（EIA）和逆转录聚合酶链反应（RT-PCR）测定细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）的表面表达和mRNA水平。通过黏附试验评估U937对HAECs的黏附情况。用7-KC孵育HAECs会增加HAECs上ICAM-1和VCAM-1的蛋白质表面表达和mRNA水平以及HAECs中活性氧（ROS）的产生。用阿拉普利预处理可剂量依赖性地降低这些分子的增强表达。阿拉普利对7-KC或TNF-α诱导的细胞黏附分子（CAMs）表达的抑制作用强于卡托普利或依那普利。阿拉普利抑制7-KC或TNF-α刺激的HAECs中ROS的产生。这些结果表明，阿拉普利通过抑制7-KC和TNF-α诱导的内皮依赖性单核细胞黏附相互作用，起到抗动脉粥样硬化剂的作用。
