Pickworth, J.A. orcid.org/0000-0002-7199-364X, Rothman, A., Iremonger, J. et al. (9 more authors) (2017) EXPRESS: Differential IL-1 signalling induced by BMPR2 deficiency drives pulmonary vascular remodelling. Pulmonary Circulation, 7 (4). pp. 768-776. ISSN 2045-8932
Abstract
Background: Bone morphogenetic protein receptor type 2 (BMPR2) mutations are present in patients with heritable and idiopathic pulmonary arterial hypertension (PAH). Circulating levels of Interleukin-1 (IL-1) are raised in patients and animal models. Whether interplay between BMP and IL- 1 signalling can explain the local manifestation of PAH in the lung remains unclear. Methods: Cell culture, siRNA and mRNA microarray analysis of RNA isolated from human Pulmonary artery (PASMC) and Aortic (AoSMC) smooth muscle cells were used. R899X+/- BMPR2 transgenic mice fed western diet for six weeks were given daily injections of IL-1ß prior to assessment for PAH and tissue collection. Results: PASMC have reduced inflammatory activation in response to IL-1ß compared with AoSMCs, however PASMC with reduced BMPR2 demonstrated an exaggerated response. Mice treated with IL-1ß had higher white blood cell counts, and significantly raised serum protein levels of IL-6 and OPG plasma levels recapitulating in vitro data. Phenotypically, IL-1ß treated mice demonstrated increased pulmonary vascular remodelling. Conclusions: IL-1ß induces an exaggerated pulmonary artery specific transcriptomic inflammatory response when BMPR2 signalling is reduced.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Sage. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Interleukin-1ß; Pulmonary hypertension; Inflammation; BMPR-II |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number BRITISH HEART FOUNDATION FS/13/48/30453 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Aug 2017 10:09 |
Last Modified: | 03 Nov 2023 16:56 |
Status: | Published |
Publisher: | Sage |
Refereed: | Yes |
Identification Number: | 10.1177/2045893217729096 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:120642 |