Notch3 signaling and vascular remodeling in pulmonary arterial hypertension

Morris, H., Neves, K. B. , Montezano, A. C., Maclean, M. R. and Touyz, R. (2019) Notch3 signaling and vascular remodeling in pulmonary arterial hypertension. Clinical Science, 133(24), pp. 2481-2498. (doi: 10.1042/CS20190835) (PMID:31868216) (PMCID:PMC6928565)

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Abstract

Notch signalling is critically involved in vascular morphogenesis and function. Four Notch isoforms (Notch1–4) regulating diverse cellular processes have been identified. Of these, Notch3 is expressed almost exclusively in vascular smooth muscle cells (VSMCs), where it is critically involved in vascular development and differentiation. Under pathological conditions, Notch3 regulates VSMC switching between the contractile and synthetic phenotypes. Abnormal Notch3 signalling plays an important role in vascular remodelling, a hallmark of several cardiovascular diseases, including pulmonary arterial hypertension (PAH). Because of the importance of Notch3 in VSMC (de)differentiation, Notch3 has been implicated in the pathophysiology of pulmonary vascular remodelling in PAH. Here we review the current literature on the role of Notch in VSMC function with a focus on Notch3 signalling in pulmonary artery VSMCs, and discuss potential implications in pulmonary artery remodelling in PAH.

Item Type:Articles
Additional Information:This work was supported by the MRC Fellowship [grant number MR/R502327/1 (to H.E.M.)]; the British Heart Foundation [grant numbers CH/12/429762, RE/13/5/30177 (to R.M.T.)]; the Walton Fellowship, University of Glasgow (to A.C.M.); and the British Heart Foundation [grant number RG/16/2/32153 (to M.R.M.)].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montezano, Dr Augusto and Neves, Dr Karla and Touyz, Professor Rhian and Morris, Hannah
Authors: Morris, H., Neves, K. B., Montezano, A. C., Maclean, M. R., and Touyz, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press on behalf of the Biochemical Society
ISSN:0143-5221
ISSN (Online):1470-8736
Copyright Holders:Copyright © 2019 The Author(s)
First Published:First published in Clinical Science 133(24):2481-2498
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190615Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762Institute of Cardiovascular & Medical Sciences
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences