The effect of AMP-activated protein kinase and its activator AICAR on the metabolism of human umbilical vein endothelial cells

In several non-vascular tissues in which it has been studied, AMP-activated protein kinase (AMPK) appears to modulate the cellular response to stresse s such as ischemia. In liver and muscle, it phosphorylates and inhibits ace tyl CoA carboxylase (ACC), leading to an increase in fatty acid oxidation; and in muscle, its activation is associated with an increase in glucose tra nsport. Here we report the presence of both AMPK and ACC in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with 2 mM AICAR, an AM PK activator, caused a 5-fold activation of AMPK, which was accompanied by a 70% decrease in ACC activity and a 2-fold increase in fatty acid oxidatio n. Surprisingly, glucose uptake and glycolysis, the dominant energy-produci ng pathway in HUVEC, were diminished by 40-60%. Despite this, cellular ATP levels were increased by 35%. Thus activation of AMPK. by AICAR is associat ed with major alterations in endothelial cell energy balance. Whether these alterations protect the endothelium during ischemia or other stresses rema ins to be determined. (C) 1999 Academic Press.