AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress

Yingjia Zhang, Tzong Shyuan Lee, Erik M. Kolb, Kai Sun, Xiao Lu, Frances M. Sladek, Ghassan S. Kassab, Theodore Garland, John Y J Shyy

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

OBJECTIVE - The regulation of AMP-activated protein kinase (AMPK) is implicated in vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS). In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a mouse model with a high level of voluntary running (High-Runner). METHODS AND RESULTS - By using flow channels with cultured ECs, AMPK Thr172 phosphorylation was increased with changes of flow rate or pulsatility. The activity of LKB1, the upstream kinase of AMPK, and the phosphorylation of eNOS at Ser1179 were concomitant with AMPK activation responding to changes in flow rate or pulsatility. The blockage of AMPK by a dominant-negative mutant of AMPK inhibited shear stress-induced eNOS Ser1179 phosphorylation and NO production. Furthermore, aortic AMPK activity and level of eNOS phosphorylation were significantly elevated in the aortas of High-Runner mice. CONCLUSIONS - Our results suggest that shear stress activates AMPK in ECs, which contributes to elevated eNOS activity and subsequent NO production. Hence, AMPK, in addition to serving as an energy sensor, also plays an important role in regulating vascular tone.

Original languageEnglish (US)
Pages (from-to)1281-1287
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume26
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • AMPK
  • Endothelium
  • Exercise
  • Nitric oxide synthase
  • Shear stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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