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Differential IL-1 signaling induced by BMPR2 deficiency drives pulmonary vascular remodeling.

Published version
Peer-reviewed

Type

Article

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Authors

Pickworth, Josephine 
Rothman, Alexander 
Iremonger, James 
Casbolt, Helen 
Hopkinson, Kay 

Abstract

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 signaling can explain the local manifestation of PAH in the lung remains unclear. 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 a Western diet for six weeks were given daily injections of IL-1ß prior to assessment for PAH and tissue collection. 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 osteoprotegerin (OPG) plasma levels recapitulating in vitro data. Phenotypically, IL-1ß treated mice demonstrated increased pulmonary vascular remodeling. IL-1ß induces an exaggerated pulmonary artery specific transcriptomic inflammatory response when BMPR2 signaling is reduced.

Description

Keywords

BMPR-II, inflammation, interleukin-1ß, pulmonary hypertension

Journal Title

Pulmonary Circulation

Conference Name

Journal ISSN

2045-8940
2045-8940

Volume Title

7

Publisher

SAGE
Sponsorship
British Heart Foundation (None)