作者
Sandro Satta, Robert Beal, Rhys Smith, Xing Luo, Glenn R Ferris, Alex Langford-Smith, Jack Teasdale, Tom Tanjeko Ajime, Jef Serré, Georgina Hazell, Graciela Sala Newby, Jason L Johnson, Svitlana Kurinna, Martin J Humphries, Ghislaine Gayan-Ramirez, Peter Libby, Hans Degens, Bo Yu, Thomas Johnson, Yvonne Alexander, Haibo Jia, Andrew C Newby, Stephen J White
发表日期
2023/7
期刊
Cardiovascular research
卷号
119
期号
9
页码范围
1869-1882
出版商
Oxford University Press
简介
Aims
Endothelial erosion of plaques is responsible for ∼30% of acute coronary syndromes (ACS). Smoking is a risk factor for plaque erosion, which most frequently occurs on the upstream surface of plaques where the endothelium experiences elevated shear stress. We sought to recreate these conditions in vitro to identify potential pathological mechanisms that might be of relevance to plaque erosion.
Methods and results
Culturing human coronary artery endothelial cells (HCAECs) under elevated flow (shear stress of 7.5 Pa) and chronically exposing them to cigarette smoke extract (CSE) and tumour necrosis factor-alpha (TNFα) recapitulated a defect in HCAEC adhesion, which corresponded with augmented Nrf2-regulated gene expression. Pharmacological activation or adenoviral overexpression of Nrf2 triggered endothelial detachment, identifying Nrf2 as a mediator of …
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S Satta, R Beal, R Smith, X Luo, GR Ferris… - Cardiovascular research, 2023