GATA4-Twist1 Signalling in Disturbed Flow-Induced Atherosclerosis.

Cardiovascular Drugs and Therapy
Marwa MahmoudPaul Evans

Abstract

Endothelial cell (EC) dysfunction (enhanced inflammation, proliferation and permeability) is the initial trigger for atherosclerosis. Atherosclerosis shows preferential development near branches and bends exposed to disturbed blood flow. By contrast, sites that are exposed to non-disturbed blood flow are atheroprotected. Disturbed flow promotes atherosclerosis by promoting EC dysfunction. Blood flow controls EC function through transcriptional and post-transcriptional mechanisms that are incompletely understood. We identified the developmental transcription factors Twist1 and GATA4 as being enriched in EC at disturbed flow, atheroprone regions of the porcine aorta in a microarray study. Further work using the porcine and murine aortae demonstrated that Twist1 and GATA4 expression was enhanced at the atheroprone, disturbed flow sites in vivo. Using controlled in vitro flow systems, the expression of Twist1 and GATA4 was enhanced under disturbed compared to non-disturbed flow in cultured cells. Disturbed flow promoted Twist1 expression through a GATA4-mediated transcriptional mechanism as revealed by a series of in vivo and in vitro studies. GATA4-Twist1 signalling promoted EC proliferation, inflammation, permeability and endothe...Continue Reading

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Citations

Jan 4, 2020·European Heart Journal·Stevan D StojanovićDaniel G Sedding
Mar 22, 2019·Cardiovascular Drugs and Therapy·David J Grieve
Oct 19, 2021·Frontiers in Cell and Developmental Biology·Tendai HunyenyiwaAkiko Mammoto

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