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Arterioscler Thromb Vasc Biol. 2016 Oct;36(10):2038-47. doi: 10.1161/ATVBAHA.116.306926. Epub 2016 Aug 25.

Delta-Like Ligand 4-Notch Signaling in Macrophage Activation.

Author information

1
From The Center for Excellence in Vascular Biology (T.N., D.F., J.K., M.A.), The Center for Interdisciplinary Cardiovascular Sciences (M.A.), Cardiovascular Division (T.N., D.F., J.K., M.A.), and Channing Division of Network Medicine (M.A.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
2
From The Center for Excellence in Vascular Biology (T.N., D.F., J.K., M.A.), The Center for Interdisciplinary Cardiovascular Sciences (M.A.), Cardiovascular Division (T.N., D.F., J.K., M.A.), and Channing Division of Network Medicine (M.A.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. maikawa@rics.bwh.harvard.edu.

Abstract

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.

KEYWORDS:

atherosclerosis; fatty liver; inflammation; macrophage; metabolic disease; veins

PMID:
27562914
PMCID:
PMC5033717
DOI:
10.1161/ATVBAHA.116.306926
[Indexed for MEDLINE]
Free PMC Article

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