@article{24f9a5338fd0425db859a2efef19e29c,
title = "Loss of the adaptor protein ShcA in endothelial cells protects against monocyte macrophage adhesion, LDL-oxydation, and atherosclerotic lesion formation",
abstract = "ShcA is an adaptor protein that binds to the cytoplasmic tail of receptor tyrosine kinases and of the Low Density Lipoprotein-related receptor 1 (LRP1), a trans-membrane receptor that protects against atherosclerosis. Here, we examined the role of endothelial ShcA in atherosclerotic lesion formation. We found that atherosclerosis progression was markedly attenuated in mice deleted for ShcA in endothelial cells, that macrophage content was reduced at the sites of lesions, and that adhesion molecules such as the intercellular adhesion molecule-1 (ICAM-1) were severely reduced. Our data indicate that transcriptional regulation of ShcA by the zinc-finger E-box-binding homeobox 1 (ZEB1) and the Hippo pathway effector YAP, promotes ICAM-1 expression independently of p-NF-κB, the primary driver of adhesion molecules expressions. In addition, ShcA suppresses endothelial Akt and nitric oxide synthase (eNOS) expressions. Thus, through down regulation of eNOS and ZEB1-mediated ICAM-1 up regulation, endothelial ShcA promotes monocyte-macrophage adhesion and atherosclerotic lesion formation. Reducing ShcA expression in endothelial cells may represent an obvious therapeutic approach to prevent atherosclerosis.",
author = "Jaoude, {Antoine Abou} and Lise Badiqu{\'e} and Mohamed Mlih and Sara Awan and Sunning Guo and Alexandre Lemle and Clauda Abboud and Sophie Foppolo and Lionel Host and J{\'e}r{\^o}me Terrand and H{\'e}l{\`e}ne Justiniano and Joachim Herz and Matz, {Rachel L.} and Philippe Boucher",
note = "Funding Information: We are grateful to Daniel Metzger (IGBMC, University of Strasbourg) for critical reading of the manuscript, V{\'e}ronique Bruban (UMR CNRS 7213, University of Strasbourg) for technical assistance, Masashi Yanagisawa (University of Texas Southwestern Medical Center, at Dallas) for kindly providing us with the Tie2Cre mice, Sophie Martin (UMR CNRS 7213, University of Strasbourg) for Human endothelial cells (EAhy), Florence Toti (UMR CNRS 7213, University of Strasbourg) for providing us with THP-1 cells, and Irwin Davidson (IGBMC, University of Strasbourg) for YAP antibodies. This work was supported by grants from Fondation de France, Fondation pour la Recherche M{\'e}dicale (FRM), the Agence Nationale de la Recherche (ANR-06-Physio-032-01 and ANR-09-BLAN-0121-01), National Institutes of Health Grants HL063762, NS093382 and AG053391 (to J.H.), the Consortium for Frontotemporal Dementia Research, and the Bright Focus Foundation. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-22819-3",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}