title: Delta-Like Ligand 4-Notch Signaling in Macrophage Activation.
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.
authors: 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.
authors: Toshiaki
authors: T
authors: Nakano
authors: 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.
authors: Daiju
authors: D
authors: Fukuda
authors: 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.
authors: Jun-Ichiro
authors: J
authors: Koga
authors: 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.
authors: Masanori
authors: M
authors: Aikawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins; D002318:Cardiovascular Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002319:Cardiovascular System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009024:Morphogenesis; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch
keywords: atherosclerosis; fatty liver; inflammation; macrophage; metabolic disease; veins