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Adv Exp Med Biol. 2010;661:279-98. doi: 10.1007/978-1-60761-500-2_18.

Notch signaling in pulmonary hypertension.

Author information

  • 1Division of Cardiothoracic Surgery, University of California, San Diego, CA, 92103-8892, USA. pthistlethwaite@ucsd.edu

Abstract

Proteins of the Notch receptor family are cell surface receptors that transduce signals between neighboring cells. The Notch signaling pathway is highly evolutionarily conserved and critical for cell fate determination during embryogenesis and early postnatal life, including many aspects of vascular development. The interaction of Notch receptor with its membrane-bound ligands leads to cleavage of the receptor into an intracellular domain that translocates to the nucleus and activates the transcription factor, C-promoter binding factor 1 (CBF1; also known as Recombination signal-binding protein for immunoglobulin kappa J region, RBPJ). To date, four Notch receptors have been characterized in humans. Of these, Notch3 is expressed only in arterial smooth muscle cells in the human. The functional importance of Notch3 signaling in human vascular smooth muscle cells has been recognized. Notch3 receptor signaling has been shown in several model systems to control vascular smooth muscle cell proliferation and maintain smooth muscle cells in an undifferentiated state. This review focuses on recent findings of the role of Notch3 in regulating vascular smooth muscle cell behavior and phenotype and discusses the potential role of Notch3 signaling in the genesis of pulmonary arterial hypertension.

PMID:
20204737
[PubMed - indexed for MEDLINE]
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