Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 36, Issue 10, Pages 2038-2047Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.116.306926
Keywords
atherosclerosis; fatty liver; inflammation; macrophage; metabolic disease; veins
Categories
Funding
- National Institutes of Health [R01HL66086, R01HL107550, R01HL126901]
- American Heart Association
- Japanese Heart Foundation/Bayer Japan
- Japan Society for the Promotion of Science
- Uehara Memorial Foundation
- Banyu Fellowship Program from the Banyu Life Science Foundation International
- American Heart Association Postdoctoral Fellowship
- International Research Fund for Subsidy of Kyushu University School of Medicine Alumni
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The Notch signaling pathway regulates the development of various cell types and organs, and also contributes to disease mechanisms in adults. Accumulating evidence suggests its role in cardiovascular and metabolic diseases. Notch signaling components also control the phenotype of immune cells. Delta-like ligand 4 (Dll4) of the Notch pathway promotes proinflammatory activation of macrophages in vitro and in vivo. Dll4 blockade attenuates chronic atherosclerosis, vein graft disease, vascular calcification, insulin resistance, and fatty liver in mice. The Dll4-Notch axis may, thus, participate in the shared mechanisms for cardiometabolic disorders, serving as a potential therapeutic target for ameliorating these global health problems.
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