Identification of atheroprone shear stress responsive regulatory elements in endothelial cells

Cardiovascular Research
Olga BondarevaHans-J Schnittler

Abstract

Oscillatory shear stress (OSS) is an atheroprone haemodynamic force that occurs in areas of vessel irregularities and is implicated in the pathogenesis of atherosclerosis. Changes in signalling and transcriptional programme in response to OSS have been vigorously studied; however, the underlying changes in the chromatin landscape controlling transcription remain to be elucidated. Here, we investigated the changes in the regulatory element (RE) landscape of endothelial cells under atheroprone OSS conditions in an in vitro model. Analyses of H3K27ac chromatin immunoprecipitation-Seq enrichment and RNA-Seq in primary human umbilical vein endothelial cells 6 h after onset of OSS identified 2806 differential responsive REs and 33 differentially expressed genes compared with control cells kept under static conditions. Furthermore, gene ontology analyses of putative RE-associated genes uncovered enrichment of WNT/HIPPO pathway and cytoskeleton reorganization signatures. Transcription factor (TF) binding motif analysis within RE sequences identified over-representation of ETS, Zinc finger, and activator protein 1 TF families that regulate cell cycle, proliferation, and apoptosis, implicating them in the development of atherosclerosis. ...Continue Reading

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Citations

Mar 30, 2019·Cardiovascular Research·Jovana Serbanovic-CanicPaul C Evans
Sep 17, 2020·Clinical Science·Yoshito Yamashiro, Hiromi Yanagisawa
Aug 1, 2020·Nature Communications·Kevin BruloisEugene C Butcher
Jul 25, 2020·Cardiovascular Research·Albano C Meli
Mar 10, 2020·Cardiology Research and Practice·Zhuhui HuangRan Dong
Aug 2, 2019·Nature Reviews. Cardiology·Celine SouilholPaul C Evans
Jul 8, 2020·International Journal of Molecular Sciences·Olga Bondareva, Bilal N Sheikh
Feb 4, 2021·Biochemical and Biophysical Research Communications·AFang LiDangheng Wei
Feb 6, 2021·Cytoskeleton·Keiichiro TanakaMartin A Schwartz

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