REVIEW article
Front. Immunol.
Sec. Inflammation
Macrophage-Driven Immunopathology in Pulmonary Arterial Hypertension: From Mechanisms to Targeted Therapies
Provisionally accepted
- 1Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
- 2Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
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Pulmonary arterial hypertension (PAH) is a progressive vascular disorder characterized by obstructive vascular remodeling driven by the aberrant proliferation of endothelial cells, smooth muscle cells, and adventitial fibroblasts within the small pulmonary arteries. Emerging evidence highlights a pivotal role for macrophage polarization in PAH pathogenesis. In the pulmonary vasculature, macrophages drive local inflammation and fibrosis through M1/M2 polarization, while the inflammatory mediators they release can also alter the systemic immune environment and indirectly influence right ventricular remodeling through the “lung–heart immune axis.” This phenotypic plasticity is tightly governed by hypoxia-induced signaling pathways, metabolic reprogramming, and epigenetic modifications. Elucidating these mechanisms has revealed macrophage polarization and immunometabolic regulation as promising therapeutic targets for PAH. Future investigations focusing on macrophage heterogeneity, single-cell transcriptomics, and precision immunomodulatory strategies are expected to accelerate the development of targeted therapies and improve clinical outcomes in PAH.
Keywords: epigenetic modifications, Macrophage polarization, metabolic reprogramming, pulmonary arterial hypertension, Pulmonary vascular remodeling, therapeutic targets
Received: 13 Oct 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Xu, Shen, Wan and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiawei Guo
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