Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 341, Issue 4, Pages 1244-1251Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.01.089
Keywords
apoptosis; endothelium; gene expression; shear stress; transcription factor
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Funding
- NHLBI NIH HHS [HL 043026, HL 080518, HL 064382] Funding Source: Medline
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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 Kruppel-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. (c) 2006 Elsevier Inc. All rights reserved.
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