2005
DOI: 10.1016/s0002-9440(10)63002-7
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Endothelial KLF2 Links Local Arterial Shear Stress Levels to the Expression of Vascular Tone-Regulating Genes

Abstract: Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridizatio… Show more

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Cited by 323 publications
(321 citation statements)
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“…In vitro, EC show induced expression of the shear stress marker KLF2 in response to high shear forces. The repressive properties of this transcription factor on the expression of, e.g., ET1 (Dekker et al, 2005), which was reflected in the inversed expression patterns in the embryonic heart and vessels (Groenendijk et al, 2004), was recapitulated in vitro (this study). Moreover, fluid shear stress repressed expression of ECE1, the enzyme that activates pro-endothelin by proteolitic cleavage.…”
Section: Discussionmentioning
confidence: 78%
See 1 more Smart Citation
“…In vitro, EC show induced expression of the shear stress marker KLF2 in response to high shear forces. The repressive properties of this transcription factor on the expression of, e.g., ET1 (Dekker et al, 2005), which was reflected in the inversed expression patterns in the embryonic heart and vessels (Groenendijk et al, 2004), was recapitulated in vitro (this study). Moreover, fluid shear stress repressed expression of ECE1, the enzyme that activates pro-endothelin by proteolitic cleavage.…”
Section: Discussionmentioning
confidence: 78%
“…This regulation apparently aims to level off shear stress, through activation or repression of vasoactive genes like endothelial nitric oxide synthase (eNOS, NOS3) or endothelin-1 (ET1), and modulate the activation state of the cells. In this respect, the zinc finger transcription factor Krü ppel-like factor-2 (KLF2/LKLF) plays a central role, in vitro (SenBanerjee et al, 2004), as well as in vivo in the adult (Lee et al, 2006;Dekker et al, 2005Dekker et al, , 2006 and embryonic vasculature (Groenendijk et al, 2004(Groenendijk et al, , 2005. KLF2 is expressed in areas of high and steady or pulsatile flow where it positively regulates eNOS and downregulates ET1, whereas prolonged oscillatory flow suppresses KLF2 expression (Wang et al, 2006).…”
Section: Introductionmentioning
confidence: 99%
“…Reduced expression of KLF2 and its transcriptional target progressively increased throughout cold storage. Although it is well established that within the liver, as well as in the vasculature, the expression of KLF2 is mainly endothelial, 11,26,27 we further characterized the effects of shear stress termination Fig. 3.…”
Section: Discussionmentioning
confidence: 99%
“…HUVECs are both phenotypically consistent and one of the most extensively used cell culture models for study of flow‐mediated EC signaling, including numerous studies of flow responses of the arterial system17, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 (eg, atheroprone versus atheroprotective waveforms) and DNMT1‐dependent DNA methylation 17, 18. For each set of experimental comparisons, cells were used from the same cell line between subculture passages 2 to 3.…”
Section: Methodsmentioning
confidence: 99%