TGFβ and BMPRII signalling pathways in the pathogenesis of pulmonary arterial hypertension.
Journal
Drug discovery today
ISSN: 1878-5832
Titre abrégé: Drug Discov Today
Pays: England
ID NLM: 9604391
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
31
08
2018
revised:
06
11
2018
accepted:
04
12
2018
pubmed:
12
12
2018
medline:
26
7
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
Pulmonary arterial hypertension (PAH) is a severe condition characterised by remodelling of precapillary pulmonary arteries sometimes associated with mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene. Even in the absence of BMPR2 mutations, increased transforming growth factor (TGF)β receptor signalling and decreased BMPRII signalling have been shown to contribute to PAH pathogenesis. In this Keynote, we review the potential mechanisms by which the imbalance of BMP/TGFβ signalling contributes to endothelial dysfunction, vascular remodelling, inflammation and disordered angiogenesis in PAH. Additionally, we highlight how currently used drugs can influence BMP/TGFβ signalling. Finally, we browse the newly developed therapeutic approaches targeting BMPRII and TGFβ signalling pathways by focusing on preclinical studies and clinical trials and put them into perspectives.
Identifiants
pubmed: 30529762
pii: S1359-6446(18)30301-5
doi: 10.1016/j.drudis.2018.12.001
pii:
doi:
Substances chimiques
Transforming Growth Factor beta
0
Bone Morphogenetic Protein Receptors, Type II
EC 2.7.11.30
Types de publication
Journal Article
Review
Langues
eng
Pagination
703-716Informations de copyright
Copyright © 2018 Elsevier Ltd. All rights reserved.