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

Abstract

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.