HIGH-DENSITY-LIPOPROTEINS INHIBIT CYTOKINE-INDUCED EXPRESSION OF ENDOTHELIAL-CELL ADHESION MOLECULES
HIGH-DENSITY-LIPOPROTEINS INHIBIT CYTOKINE-INDUCED EXPRESSION OF ENDOTHELIAL-CELL ADHESION MOLECULES
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DOI：
10.1161/01.atv.15.11.1987
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发表时间：
1995-11-01
影响因子：
8.7
通讯作者：
BARTER, PJ
中科院分区：
文献类型：
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作者：
COCKERILL, GW;RYE, KA;BARTER, PJ
虽然HDL的血浆浓度升高可防止动脉粥样硬化和随后的冠心病（CHD）的发展，但这种保护的机制尚不清楚。动脉粥样硬化形成的一个早期细胞事件是单核白细胞与内皮细胞的粘附。该事件主要由血管细胞粘附分子-1（VCAM-1）介导，但也涉及其他分子，如细胞间粘附分子-1（ICAM-1）和E-选择素。我们研究了分离的血浆HDL和重组HDL对内皮细胞表达这些分子的影响。我们发现，生理浓度的HDL抑制肿瘤坏死因子或（TNF-α）或白细胞介素-1（IL-1）诱导这些白细胞粘附分子的浓度依赖性的方式。TNF-α诱导的VCAM-1和E-选择素的稳态mRNA水平被生理浓度的HDL显著降低。在HDL浓度为1 mg/mL的载脂蛋白A-I时，VCAM-1的蛋白质表达。ICAM-1和E-选择素的抑制率分别为89.6+/-0.4%（mean+/-SD，n=4）、64.8+/-1.0%和79.2+/-0.4%。相反，HDL对血小板内皮细胞粘附分子（PECAM）的表达或TNF-α受体的p55和p75亚基的表达没有影响。HDL在细胞因子刺激前16小时至刺激后5分钟加入时有效。HDL对TNF-α诱导的人包皮成纤维细胞ICAM-1的表达没有影响;这表明这种影响是细胞类型限制的。这项研究提供了第一个证据表明，高密度脂蛋白可以通过抑制粘附分子的表达，这是白细胞和内皮细胞之间的相互作用所必需的，以防止冠心病。
While an elevated plasma concentration of HDLs is protective against the development of atherosclerosis and ensuing coronary heart disease (CHD), the mechanism of this protection is unknown. One early cellular event in atherogenesis is the adhesion of mononuclear leukocytes to the endothelium. This event is mediated principally by vascular cell adhesion molecule-1 (VCAM-1) but also involves other molecules, such as intercellular adhesion molecule-1 (ICAM-1) and E-selectin. We have investigated the effect of isolated plasma HDLs and reconstituted HDLs on the expression of these molecules by endothelial cells. We show that physiological concentrations of HDLs inhibit tumor necrosis factor-or (TNF-alpha) or interleukin-1 (IL-1) induction of these leukocyte adhesion molecules in a concentration-dependent manner. Steady state mRNA levels of TNF-alpha-induced VCAM-1 and E-selectin are significantly reduced by physiological concentrations of HDLs. At an HDL concentration of 1 mg/mL apolipoprotein A-I, the protein expressions of VCAM-1. ICAM-1, and E-selectin were inhibited by 89.6+/-0.4% (mean+/-SD, n=4), 64.8+/-1.0%, and 79.2+/-0.4%, respectively. In contrast, HDLs have no effect on the expression of platelet endothelial cell adhesion molecule (PECAM) or on the expression of the p55 and p75 subunits of the TNF-alpha receptor. HDLs were effective when added from 16 hours before to 5 minutes after cytokine stimulation. HDLs had no effect on TNF-alpha-induced expression of ICAM-1 by human foreskin fibroblasts; suggesting that the effect is cell-type restricted. This study provides the first evidence that HDLs may protect against CHD by inhibiting the expression of adhesion molecules, which are required for the interaction between leukocytes and the endothelium.