ArticleERJ open research2025
Reversal of inflammatory reprogramming by vasodilator agents in pulmonary hypertension.
Article in ERJ open research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
13 authors.
Funding
Abstract
Background: Pulmonary arterial hypertension (PAH) is a deadly disease without effective non-invasive diagnostic and prognostic testing. It remains unclear whether vasodilators reverse inflammatory activation, a part of PAH pathogenesis. Single-cell profiling of inflammatory cells in blood could clarify these PAH mechanisms. Methods: We evaluated a University of Pittsburgh Medical Center cohort consisting of idiopathic PAH (iPAH) and systemic sclerosis-associated PAH (sscPAH) patients and non-PAH controls. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from controls (n=3) and from PAH patients (iPAH and sscPAH) naïve to treatment (n=4), PAH patients 3 months after phosphodiesterase-5 inhibitor (PDE5i) treatment (n=7) and PAH patients 3 months after PDE5i+macitentan treatment (n=6). We compared the transcriptomes of five PBMC subtypes from iPAH and sscPAH to observe their serial responses to treatments. Furthermore, we utilised network analysis to illuminate the altered connectivity of biological networks in this complex disease. Results: We defined differential gene expression and perturbed network connectivity in PBMCs of PAH patients following treatment with PDE5i or PDE5i+macitentan. Importantly, we identified significant reversal of inflammatory transcripts and pathways in the combined PAH patient cohort after vasodilator therapy in every PBMC type assessed. The "glucagon signalling in metabolic regulation" pathway in monocytes was reversed after vasodilator therapy Conclusion:
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