TGF-β in vascular pathobiology

Schwartze, J. T., Low, E. L. and Bradshaw, A. C. (2019) TGF-β in vascular pathobiology. In: Touyz, R. M. and Delles, C. (eds.) Textbook of Vascular Medicine. Springer: Cham, pp. 137-148. ISBN 9783030164805 (doi: 10.1007/978-3-030-16481-2_13)

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Abstract

The transforming growth factor (TGF)-β superfamily includes 32 cytokines that tightly regulate vascular cell behaviour such as proliferation, migration, apoptosis, differentiation and extracellular matrix (ECM) maintenance, production and remodelling. Superfamily ligands signal via distinct type I and type II transmembrane serine/threonine kinase receptors activating canonical receptor-regulated (R)-s-mothers against decapentaplegic (SMAD) signalling and non-canonical signalling pathways. Normal vascular morphogenesis and homeostasis depend on intact TGF-β superfamily signalling. Genetic studies have demonstrated that defects in genes encoding TGF-β superfamily members predispose or are causally linked to certain hereditary vascular disorders (HVDs) such as hereditary haemorrhagic telangiectasia (HHT), hereditary pulmonary arterial hypertension (HPAH) and Loeys-Dietz syndrome (LDS). These discoveries have led to a better understanding of HVD pathogenesis giving rise to novel drug treatment strategies continuously improving life expectancy and the quality of life of affected patients. In addition, recent studies have discovered that the type I receptor activin-like kinase (ALK)1 and the type III co-receptor endoglin (ENG) promote tumour angiogenesis prompting the development of the ALK1 ligand trap dalantercept, the neutralising ALK1 antibody PF-03446962 and the monoclonal ENG antibody carotuximab. These novel anti-angiogenic cancer drugs have been or are currently being tested in phase I, II and III clinical trials for patients with advanced solid tumours.

Item Type:Book Sections
Status:Published
Glasgow Author(s) Enlighten ID:Schwartze, Mr Julian and Bradshaw, Dr Angela and Low, Emma
Authors: Schwartze, J. T., Low, E. L., and Bradshaw, A. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Publisher:Springer
ISBN:9783030164805
Published Online:03 August 2019

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