Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific

Biochem Biophys Res Commun. 2006 Mar 24;341(4):1244-51. doi: 10.1016/j.bbrc.2006.01.089. Epub 2006 Jan 30.


Flow patterns in blood vessels contribute to focal distribution of atherosclerosis; the underlying mechanotransduction pathways remain to be investigated. We demonstrate that different flow patterns elicit distinct responses of Krüppel-like factor-2 (KLF2) in endothelial cells (ECs) in vitro and in vivo. While pulsatile flow with a significant forward direction induced sustained expression of KLF2 in cultured ECs, oscillatory flow with little forward direction caused prolonged suppression after a transient induction. The suppressive effect of oscillatory flow was Src-dependent. Immunohistochemical studies on ECs at arterial branch points revealed that KLF2 protein levels were related to local hemodynamics. Such flow-associated expression patterns were also demonstrated in a rat aortic restenosis model. Inhibition of KLF2 with siRNA sensitized ECs to oxidized LDL-induced apoptosis, indicating a protective role of KLF2. In conclusion, differential regulation of KLF2 may mediate the distinct vascular effects induced by various patterns of shear stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Abdominal / physiology
  • Aortic Valve Stenosis / physiopathology
  • Apoptosis / drug effects
  • Celiac Artery / physiology
  • Cells, Cultured
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / physiology*
  • Gene Expression Regulation
  • Hemodynamics
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / deficiency
  • Male
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Mechanical
  • Umbilical Veins
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / physiology


  • 4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • Pyrazoles
  • Pyrimidines
  • src-Family Kinases