Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2.

@article{Fledderus2007ProlongedSS,
  title={Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2.},
  author={Joost O. Fledderus and Johannes V. van Thienen and Reinier A. Boon and Rob J. Dekker and Jakub Rohlena and Oscar L. Volger and Ann Pascale Bijnens and Mat J.A.P. Daemen and Johan Kuiper and Th J C van Berkel and H. Pannekoek and Anton J. G. Horrevoets},
  journal={Blood},
  year={2007},
  volume={109 10},
  pages={
          4249-57
        }
}
Absence of shear stress due to disturbed blood flow at arterial bifurcations and curvatures leads to endothelial dysfunction and proinflammatory gene expression, ultimately resulting in atherogenesis. KLF2 has recently been implicated as a transcription factor involved in mediating the anti-inflammatory effects of flow. We investigated the effect of shear on basal and TNF-alpha-induced genomewide expression profiles of human umbilical vein endothelial cells (HUVECs). Cluster analysis confirmed… 
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Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS.
TLDR
The results reveal that phosphorylation-dependent derepression of HDAC5 mediates flow-induced KLF2 and eNOS expression as well as flow anti-inflammation, and suggest thatHDAC5 could be a potential therapeutic target for the prevention of atherosclerosis.
Key transcriptional regulators of the vasoprotective effects of shear stress.
TLDR
The widespread beneficial effects of the key transcription factors KLF2 and Nrf2 on endothelial phenotype, holds the promise that their targeted modulation might lead to a new class of cardiovascular drugs.
Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC 5 and mediates expression of KLF 2 and eNOS
TLDR
The results reveal that phosphorylation-dependent derepression of HDAC5 mediates flow-induced KLF2 and eNOS expression as well as flow anti-inflammation, and suggest thatHDAC5 could be a potential therapeutic target for the prevention of atherosclerosis.
The metalloproteinase ADAM15 is upregulated by shear stress and promotes survival of endothelial cells.
KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium.
TLDR
Findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers.
Cigarette smoke extract profoundly suppresses TNFα-mediated proinflammatory gene expression through upregulation of ATF3 in human coronary artery endothelial cells
TLDR
It is found that laminar flow fails to overcome the inflammatory effects of TNFα under these conditions but that cigarette smoke induces an anti-oxidant response that appears to reduce endothelial inflammation, and ATF3 is identified as an important protective factor against endothelial dysfunction.
KLF2 Primes the Antioxidant Transcription Factor Nrf2 for Activation in Endothelial Cells
TLDR
KLF2 substantially enhances antioxidant activity of Nrf2 by increasing its nuclear localization and activation and the synergistic activity of these two transcription factors forms a major contribution to the shear stress–elicited transcriptome in endothelial cells.
PI16 is a shear stress and inflammation-regulated inhibitor of MMP2
TLDR
Four splice variants of the peptidase inhibitor 16 (PI16) mRNA are among the most highly shear stress regulated transcripts in human coronary artery endothelial cells, in vitro but that expression is reduced by inflammatory mediators TNFα and IL-1β.
KLF2 Upregulates miR-483 to Modulate Endothelial Function
TLDR
A genome wide search for putative KLF2 binding sequences within the regulatory regions of shear stress responsive miRNAs is performed to hypothesize that the KLf2 can directly regulate miRNA expression through binding of regulatory regions to promote or repress transcription.
Flow Activation of AMP-Activated Protein Kinase in Vascular Endothelium Leads to Krüppel-Like Factor 2 Expression
TLDR
The flow-mediated AMPK activation is a newly defined KLF2 regulatory pathway in vascular endothelium that acts via ERK5/MEF2 and was significantly reduced in the aorta of AMPKα2 knockout mice.
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References

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