Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:543-553
Published online before print February 13, 2003, doi: 10.1161/01.ATV.0000060892.81529.8F
Published online before print February 13, 2003, doi: 10.1161/01.ATV.0000060892.81529.8F
© 2003 American Heart Association, Inc.
ATVB In Focus |
Notch Signaling in Vascular Development
From the Second Department of Internal Medicine (T.I.), Gunma University School of Medicine, Gunma 371-8511, Japan; Center for Cardiovascular Development (Y.H.), Department of Medicine, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tex; and Institute for Genetic Medicine (L.K.), Department of Biochemistry and Molecular Biology, and Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles.
Correspondence to Larry Kedes, 2250 Alcazar Street, Los Angeles, CA 90089. E-mail kedes{at}hsc.usc.edu
Previous Brief Review in this Series:
Hillebrands J-L, Klatter FA, Rozing J. Origin of vascular smooth muscle cells and the role of circulating stem cells in transplant arteriosclerosis. 2003;23:380–387.
Abstract
Notch signaling is an extremely conserved and widely used mechanism regulating cell fate in metazoans. Interaction of Notch receptors (Notch) with their ligands (Delta-like or Jagged) leads to cleavage of the Notch intracellular domain (NICD) that migrates into the nucleus. In the nucleus, NICD associates with a transcription factor, RBP-Jk. The NICD-RBP-Jk complex, in turn, upregulates expression of primary target genes of Notch signaling, such as hairy and enhancer of split (HES) and HES-related repressor protein (HERP) transcriptional repressors. Recent evidence has demonstrated that the Notch pathway is involved in multiple aspects of vascular development, including proliferation, migration, smooth muscle differentiation, angiogenic processes, and arterial-venous differentiation. In this brief review, we focus on ligands, receptors, and target genes of Notch signaling in the vascular system and discuss (1) tissue distribution; (2) gain- and loss-of-function studies; and (3) the role of Notch components in human diseases involving the vascular system.
Key Words: notch signaling • smooth muscle differentiation • angiogenic processes • vascular system
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