Hyperinsulinemia is an independent risk factor for cardiovascular events and may contribute to cardio- vascular disease. Low-grade chronic inflammation has been implicated in the pathogenesis of atherosclerosis. We aimed at determining the impact of pathophysiologically high insulin concentrations on cytokine- induced endothelial activation in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with insulin (0-24 h)±tumor necrosis factor (TNF)-? or lipopolysaccharide (LPS). At pathophysiological/ pharmacological concentrations (10 - 9 -10 - 7 mol/L), insulin selectively induced VCAM-1 expression and potentiated the effects of TNF-? andLPS, effects reverted by the proteasome inhibitor lactacystin. Compared with TNF-? alone, insulin+TNF-? doubled U937 cell adhesion. Insulin markedly increased TNF-?-induced NF-?B activation and induced phosphorylated I?B-? accumulation. Therefore, hyperinsulinemia enhances cytokine-induced VCAM-1 expression in endothelial cells, thus potentially contributing to detrimental effects of other inflammatory stimuli on atherogenesis.
Insulin potentiates cytokine-induced VCAM-1 expression in human endothelial cells
Marika Massaro;
2008
Abstract
Hyperinsulinemia is an independent risk factor for cardiovascular events and may contribute to cardio- vascular disease. Low-grade chronic inflammation has been implicated in the pathogenesis of atherosclerosis. We aimed at determining the impact of pathophysiologically high insulin concentrations on cytokine- induced endothelial activation in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with insulin (0-24 h)±tumor necrosis factor (TNF)-? or lipopolysaccharide (LPS). At pathophysiological/ pharmacological concentrations (10 - 9 -10 - 7 mol/L), insulin selectively induced VCAM-1 expression and potentiated the effects of TNF-? andLPS, effects reverted by the proteasome inhibitor lactacystin. Compared with TNF-? alone, insulin+TNF-? doubled U937 cell adhesion. Insulin markedly increased TNF-?-induced NF-?B activation and induced phosphorylated I?B-? accumulation. Therefore, hyperinsulinemia enhances cytokine-induced VCAM-1 expression in endothelial cells, thus potentially contributing to detrimental effects of other inflammatory stimuli on atherogenesis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
