Endothelial TGF-beta signalling drives vascular inflammation and atherosclerosis

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; Sun, Hongye; Zhang, Xinbo; Aryal, Binod; Canfran-Duque, Alberto; Liu, Rebecca; Kusters, Pascal; Sehgal, Alfica; Jiao, Yang; Anderson, Daniel G.; Gulcher, Jeffrey; Fernandez-Hernando, Carlos; Lutgens, Esther; Schwartz, Martin A.; Pober, Jordan S.; Chittenden, Thomas W.; Tellides, George und Simons, Michael (2019): Endothelial TGF-beta signalling drives vascular inflammation and atherosclerosis. In: Nature Metabolism, Bd. 1, Nr. 9: S. 912-926

Abstract

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 beta (TGF-beta) signalling is one of the primary drivers of atherosclerosis-associated vascular inflammation. Inhibition of endothelial TGF-beta 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-beta 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch