title: Flow activation of AMP-activated protein kinase in vascular endothelium leads to Krüppel-like factor 2 expression.
abstract: 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).
  
  
  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 AMPKalpha2 knockout mice when compared with wild-type control mice.
  
  
  CONCLUSIONS
  The flow-mediated AMPK activation is a newly defined KLF2 regulatory pathway in vascular endothelium that acts via ERK5/MEF2.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Young
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Benjamin Larman
authors.forename: Harry B
authors.initials: HB
authors.lastname: Larman
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Li
authors.forename: John Y
authors.initials: JY
authors.lastname: Shyy
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Cardeña
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D015151:Immunoblotting; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010766:Phosphorylation; D011336:Probability; D011673:Pulsatile Flow / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013314:Stress, Mechanical; D014162:Transfection; D015854:Up-Regulation
chemical_list: D018076:DNA, Complementary; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D055372:AMP-Activated Protein Kinases
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