on September 18, 2008
Published online before print September 18, 2008, doi: 10.1161/ATVBAHA.108.175919
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Submitted on June 20, 2008
Accepted on September 3, 2008
Inhibition of Tumor Necrosis Factor 
–Stimulated Monocyte Adhesion to Human Aortic Endothelial Cells by AMP-Activated Protein Kinase
Marie-Ann Ewart ;
From the Henry Wellcome Laboratory for Cell Biology, Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, UK.
* To whom correspondence should be addressed. E-mail: i.salt{at}bio.gla.ac.uk.
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
-stimulated adhesion of promonocytic U-937 cells. Rapid inhibition of TNF-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-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-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.