Inhibition of tumor necrosis factor α–stimulated monocyte adhesion to human aortic endothelial cells by AMP-activated protein kinase

Ewart, M.-A., Kohlhaas, C.F. and Salt, I.P. (2008) Inhibition of tumor necrosis factor α–stimulated monocyte adhesion to human aortic endothelial cells by AMP-activated protein kinase. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(12), pp. 2255-2257. (doi: 10.1161/ATVBAHA.108.175919)

Abstract

<b>Objective</b>— 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. <b>Methods and Results</b>— HAECs incubated with the AMPK activator, AICAR, or expressing constitutively active AMPK demonstrated reduced TNF α-stimulated adhesion of promonocytic U-937 cells. Rapid inhibition of TNF α-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 α-stimulated U-937 cell adhesion by prolonged AMPK activation was NO-independent and associated with reduced cell surface adhesion molecule expression. <b>Conclusions</b>— AMPK activation in HAECs inhibits TNF α-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. We investigated the functional effects of AMPK activation in cultured human endothelial cells. Stimulation of AMPK inhibited TNF α-stimulated monocyte adhesion by two distinct mechanisms: a rapid NO-dependent mechanism associated with a reduction in chemokine release and a late NO-independent mechanism whereby adhesion molecule expression is suppressed.

• Item Type: Articles
• Keywords: AMP-activated protein kinase, endothelium, nitric oxide, adhesion
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ewart, Dr Marie-Ann and Salt, Dr Ian and Akehurst, Dr Christine
• Authors: Ewart, M.-A., Kohlhaas, C.F., and Salt, I.P.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Arteriosclerosis, Thrombosis, and Vascular Biology
• Publisher: American Heart Association
• ISSN: 1079-5642
• ISSN (Online): 1524-4636
• Published Online: 18 September 2008
• Copyright Holders: Copyright © 2008 American Heart Association
• First Published: First published in Arteriosclerosis, Thrombosis, and Vascular Biology 28(12):2255-2257
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher