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 journalArticle

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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

Fingerprint

Endothelial cells
Flow patterns
Shear stress
Endothelial Cells
Blood Vessels
Pulsatile Flow
Pulsatile flow
Blood vessels
Hemodynamics
Small Interfering RNA
Rats
Cultured Cells
Atherosclerosis
Apoptosis
Proteins
Direction compound

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, Nanping ; Miao, Hui ; Li, Yi Shuan ; Zhang, Peng ; Haga, Jason H. ; Hu, Yingli ; Young, Angela ; Yuan, Suli ; Nguyen, Phu ; Wu, Chia-Ching ; Chien, Shu. / Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 341, No. 4. pp. 1244-1251.
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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 Kr{\"u}ppel-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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Wang, N, Miao, H, Li, YS, Zhang, P, Haga, JH, Hu, Y, Young, A, Yuan, S, Nguyen, P, Wu, C-C & Chien, S 2006, 'Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific', Biochemical and Biophysical Research Communications, vol. 341, no. 4, pp. 1244-1251. https://doi.org/10.1016/j.bbrc.2006.01.089

Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific. / Wang, Nanping; Miao, Hui; Li, Yi Shuan; Zhang, Peng; Haga, Jason H.; Hu, Yingli; Young, Angela; Yuan, Suli; Nguyen, Phu; Wu, Chia-Ching; Chien, Shu.

In: Biochemical and Biophysical Research Communications, Vol. 341, No. 4, 24.03.2006, p. 1244-1251.

Research output: Contribution to journalArticle

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AU - Wang, Nanping

AU - Miao, Hui

AU - Li, Yi Shuan

AU - Zhang, Peng

AU - Haga, Jason H.

AU - Hu, Yingli

AU - Young, Angela

AU - Yuan, Suli

AU - Nguyen, Phu

AU - Wu, Chia-Ching

AU - Chien, Shu

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N2 - 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.

AB - 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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