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

Nanping Wang, Hui Miao, Yi Shuan Li, Peng Zhang, Jason H. Haga, Yingli Hu, Angela Young, Suli Yuan, Phu Nguyen, Chia Ching Wu, Shu Chien

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1244-1251
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume341
Issue number4
DOIs
Publication statusPublished - 2006 Mar 24

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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