Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide

Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It s erves 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 increas ed in inflammation and atherosclerosis. As it has been suggested that insul in and hyperinsulinemia may have a role in atherogenesis, we have now inves tigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by co llagenase digestion and were grown in culture. Insulin (100 and 1000 mu U/m L) caused a decrease in the expression of ICAM-1 (messenger ribonucleic aci d and protein) by these cells in a dose- dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in end othelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by n itric oxide (NO) from increased endothelial NOS, HAEC were treated with N-o mega-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 t he expression of the proinflammatory adhesion molecule ICAM-1 through an in crease in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.