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Recombinant human interferon alpha 2b prevents and reverses experimental pulmonary hypertension

Bauer, EM and Zheng, H and Lotze, MT and Bauer, PM (2014) Recombinant human interferon alpha 2b prevents and reverses experimental pulmonary hypertension. PLoS ONE, 9 (5).

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Pulmonary hypertension (PH) is a progressive and fatal disease with no cure. Vascular remodeling in PH involves intraluminal growth of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Cell growth in these lesions is quasi-neoplastic, with evidence of monoclonality, apoptosis resistance and cancer-like metabolic derangements. Herein we tested the effect of human interferon alpha 2b (IFNα), a pleiotropic cytokine and anti-cancer therapeutic, on the development and progression of PH in the rat SU5416/hypoxia (SUH) model and mouse hypoxia model of the disease. In both models IFNα attenuated the development of PH and reversed established PH as assessed by measuring right ventricular systolic pressure and right ventricular hypertrophy. The effect of IFNα was dependent on the type I interferon receptor (IFNAR) since mice lacking a subunit of the IFNAR were not protected by IFNα. Morphometric analysis of pulmonary aterioles from hypoxic mice or SUH rats showed that IFNα inhibited pulmonary vascular remodeling in both models and that IFNα reversed remodeling in SUH rats with established disease. Immunohistochemical staining revealed that IFNα decreased the number of PCNA and Tunel positive cells in the wall of pulmonary arterioles. In vitro, IFNα inhibited proliferation of human pulmonary artery smooth muscle cells and as well as human pulmonary artery endothelial cell proliferation and apoptosis. Together these findings demonstrate that IFNα reverses established experimental PH and provide a rationale for further exploration of the use of IFNα and other immunotherpies in PH. © 2014 Bauer et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bauer, EMemb62@pitt.eduEMB62
Zheng, H
Lotze, MTmtl5@pitt.eduMTL5
Bauer, PM
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Vascular Medicine Institute
Date: 16 May 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0096720
Schools and Programs: School of Medicine > Pharmacology and Chemical Biology
School of Medicine > Surgery
Refereed: Yes
Date Deposited: 30 Jun 2014 15:03
Last Modified: 01 Mar 2019 14:57


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