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  • Title: Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific.
    Author: Wang N, Miao H, Li YS, Zhang P, Haga JH, Hu Y, Young A, Yuan S, Nguyen P, Wu CC, Chien S.
    Journal: Biochem Biophys Res Commun; 2006 Mar 24; 341(4):1244-51. PubMed ID: 16466697.
    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.
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