Inhibition of Tumor Necrosis Factor α-Stimulated Monocyte Adhesion to Human Aortic Endothelial Cells by AMP-Activated Protein Kinase

Objective-Proatherosclerotic adhesion of leukocytes to the endothelium is attenuated by NO. As AMP-activated protein kinase (AMPK) regulates endothelial NO synthesis, we investigated the modulation of adhesion to cultured human aortic endothelial cells (HAECs) by AMPK. Methods and Results-HAECs incubated with the AMPK activator, AICAR, or expressing constitutively active AMPK demonstrated reduced TNF alpha-stimulated adhesion of promonocytic U-937 cells. Rapid inhibition of TNF alpha-stimulated U-937 cell adhesion by AICAR was NO-dependent, associated with unaltered cell surface adhesion molecule expression, and reduced MCP-1 secretion by HAECs. In contrast, inhibition of TNF alpha-stimulated U-937 cell adhesion by prolonged AMPK activation was NO-independent and associated with reduced cell surface adhesion molecule expression. Conclusions-AMPK activation in HAECs inhibits TNF alpha-stimulated leukocyte adhesion by a rapid NO-dependent mechanism associated with reduced MCP-1 secretion and a late NO-independent mechanism whereby adhesion molecule expression, in particular E-selectin, is suppressed. (Arterioscler Thromb Vasc Biol. 2008;28:2255-2257.)