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(Circulation Research. 2008;103:1370.)
© 2008 American Heart Association, Inc.

Reviews

Notch and Vascular Smooth Muscle Cell Phenotype

David Morrow, Shaunta Guha, Catherine Sweeney, Yvonne Birney, Tony Walshe, Colm O’Brien, Dermot Walls, Eileen M. Redmond, Paul A. Cahill

From the Vascular Health Research Centre (D.M., S.G., C.S., Y.B., T.W., P.A.C.), Faculty of Science and Health; and School of Biotechnology (D.W.), National Centre for Sensor Research, Dublin City University, Ireland; Department of Surgery (D.M., E.M.R.), University of Rochester, NY; Schepens Eye Research Institute (T.W.), Harvard Medical School, Boston, Mass; and Mater Misericordiae Hospital (C.O.), Institute of Ophthalmology, The Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland.

Correspondence to Paul A. Cahill, Vascular Health Research Centre, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. E-mail paul.cahill{at}dcu.ie

This Review is part of a thematic series on Notch in the Cardiovascular System, which includes the following articles:

Crosstalk Between Vascular Endothelial Growth Factor, Notch, and Transforming Growth Factor-β in Vascular Morphogenesis [2008;102:637–652]

Notch Signaling in Cardiac Development [2008;102:1169–1181]

Notch and Vascular Smooth Muscle Phenotype
Aly Karsan Guest Editor

The Notch signaling pathway is critical for cell fate determination during embryonic development, including many aspects of vascular development. An emerging paradigm suggests that the Notch gene regulatory network is often recapitulated in the context of phenotypic modulation of vascular smooth muscle cells (VSMC), vascular remodeling, and repair in adult vascular disease following injury. Notch ligand receptor interactions lead to cleavage of receptor, translocation of the intracellular receptor (Notch IC), activation of transcriptional CBF-1/RBP-J–dependent and –independent pathways, and transduction of downstream Notch target gene expression. Hereditary mutations of Notch components are associated with congenital defects of the cardiovascular system in humans such as Alagille syndrome and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Recent loss- or gain-of-function studies have provided insight into novel Notch-mediated CBF-1/RBP-J–dependent and –independent signaling and cross-regulation to other molecules that may play a critical role in VSMC phenotypic switching. Notch receptors are critical for controlling VSMC differentiation and dictating the phenotypic response following vascular injury through interaction with a triad of transcription factors that act synergistically to regulate VSMC differentiation. This review focuses on the role of Notch receptor ligand interactions in dictating VSMC behavior and phenotype and presents recent findings on the molecular interactions between the Notch components and VSMC-specific genes to further understand the function of Notch signaling in vascular tissue and disease.

Key Words: Notch • vascular phenotype • differentiation • disease

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				J. N. Regan and M. W. Majesky Building a Vessel Wall With Notch Signaling Circ. Res., February 27, 2009; 104(4): 419 - 421. [Full Text] [PDF]