Flow activation of AMP-activated protein kinase in vascular endothelium leads to Kruppel-like factor 2 expression

A Young, W Wu, W Sun, HB Larman… - … , and vascular biology, 2009 - Am Heart Assoc
A Young, W Wu, W Sun, HB Larman, N Wang, YS Li, JY Shyy, S Chien, G García-Cardeña
Arteriosclerosis, thrombosis, and vascular biology, 2009Am Heart Assoc
Objective—Vascular endothelial cells (ECs) confer atheroprotection at locations of the
arterial tree where pulsatile laminar flow (PS) exists with a high shear stress and a large net
forward direction. We investigated whether the PS-induced expression of the transcription
factor Krüppel-Like Factor 2 (KLF2) in cultured ECs and its expression in the mouse aorta
is regulated by AMP-activated protein kinase (AMPK). Methods and Results—AMPK
inhibition by Compound C or siRNA had a significant blocking effect on the PS-induced …
Objective— Vascular endothelial cells (ECs) confer atheroprotection at locations of the arterial tree where pulsatile laminar flow (PS) exists with a high shear stress and a large net forward direction. We investigated whether the PS-induced expression of the transcription factor Krüppel-Like Factor 2 (KLF2) in cultured ECs and its expression in the mouse aorta is regulated by AMP-activated protein kinase (AMPK).
Methods and Results— AMPK inhibition by Compound C or siRNA had a significant blocking effect on the PS-induced KLF2 expression. The induction of KLF2 by PS led to the increase in eNOS and the suppression of ET-1, which could be reversed by KLF2 siRNA. In addition, PS induced the phosphorylation of ERK5 and MEF2 which are necessary for the KLF2 expression. These mechanotransduction events were abrogated by the blockade of AMPK. Furthermore, the phosphorylation levels of ERK5 and MEF2, as well as the expression of KLF2, were significantly reduced in the aorta of AMPKα2 knockout mice when compared with wild-type control mice.
Conclusion— The flow-mediated AMPK activation is a newly defined KLF2 regulatory pathway in vascular endothelium that acts via ERK5/MEF2.
Am Heart Assoc