Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Name
nihms-1534929.pdf
Description
Accepted version
Size
4.09 MB
Format
Adobe PDF
Checksum (MD5)
71e22278b268fc64b49eb3b9fadadc10
Author(s)
Chen, Pei-Yu
Qin, Lingfeng
Li, Guangxin
Wang, Zheng
Dahlman, James E
Malagon-Lopez, Jose
Gujja, Sharvari
Cilfone, Nicholas A
Kauffman, Kevin J
Sun, Lele
Date Issued
2019
Journal
Nature Metabolism
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Atherosclerosis is a progressive vascular disease triggered by interplay between abnormal shear stress and endothelial lipid retention. A combination of these and, potentially, other factors leads to a chronic inflammatory response in the vessel wall, which is thought to be responsible for disease progression characterized by a buildup of atherosclerotic plaques. Yet molecular events responsible for maintenance of plaque inflammation and plaque growth have not been fully defined. Here we show that endothelial transforming growh factor β (TGF-β) signalling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGF-β signalling in hyperlipidemic mice reduces vessel wall inflammation and vascular permeability and leads to arrest of disease progression and regression of established lesions. These proinflammatory effects of endothelial TGF-β signalling are in stark contrast with its effects in other cell types and identify it as an important driver of atherosclerotic plaque growth and show the potential of cell-type-specific therapeutic intervention aimed at control of this disease.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
10.1038/S42255-019-0102-3
