Aljada A, Saadeh R, Assian E, Ghanim H, Dandona P
Division of Endocrinology, Diabetes, and Metabolism, State University of New York, Buffalo 14209, USA.
J Clin Endocrinol Metab. 2000 Jul;85(7):2572-5. doi: 10.1210/jcem.85.7.6677.
Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 microU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with N(omega)-nitro-L-arginine, a NOS inhibitor. N(omega)-Nitro-L-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.
细胞间黏附分子-1（ICAM-1）在内皮细胞和其他细胞类型中表达，并参与炎症和动脉粥样硬化过程。它作为白细胞上白细胞功能相关抗原-1的配体，部分负责淋巴细胞、粒细胞和单核细胞与细胞因子刺激的内皮细胞的黏附以及随后的跨内皮迁移。其在内皮细胞上的表达在炎症和动脉粥样硬化中增加。由于有研究表明胰岛素和高胰岛素血症可能在动脉粥样硬化的发生中起作用，我们现在研究了胰岛素是否对人主动脉内皮细胞（HAEC）上ICAM-1的表达有影响。HAEC通过胶原酶消化从人主动脉中制备，并在培养中生长。胰岛素（100和1000微单位/毫升）在孵育2天后以剂量依赖的方式导致这些细胞中ICAM-1（信使核糖核酸和蛋白质）的表达降低。这种降低与胰岛素诱导的内皮型一氧化氮合酶（NOS）表达的同时增加有关。为了研究胰岛素诱导的ICAM-1抑制是否由内皮NOS增加产生的一氧化氮（NO）介导，用NOS抑制剂N（ω）-硝基-L-精氨酸处理HAEC。N（ω）-硝基-L-精氨酸在信使核糖核酸和蛋白质水平上抑制了胰岛素诱导的HAEC中ICAM-1表达的降低。因此，胰岛素对ICAM-1表达的抑制作用是由NO介导的。我们得出结论，胰岛素通过增加NOS的表达和NO的产生来降低促炎黏附分子ICAM-1的表达，并且胰岛素可能具有潜在的抗炎和抗动脉粥样硬化作用，而不是促动脉粥样硬化作用。
