Alveolar macrophage heterogeneity in pulmonary hypertension: pathogenic mechanisms and precision intervention.

Authors

Tianfei Fan, Yao Wang, Longji Li

Published in

Journal of hypertension. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

Pulmonary hypertension (PH) involves complex interactions between immune dysfunction and pulmonary vascular remodeling. Alveolar macrophages (AMs) are important regulators linking pulmonary immune responses to vascular pathology. However, AMs are not a homogeneous population and undergo dynamic functional reprogramming in response to chronic hypoxia, endothelial injury, metabolic stress, and extracellular matrix remodeling. This review summarizes current evidence on the mechanisms and pathological roles of AM heterogeneity in PH, focusing on cellular origin, microenvironmental regulation, transcriptional control, metabolic reprogramming, and intercellular crosstalk. We further discuss how distinct AM functional states contribute to chronic inflammation, pulmonary vascular remodeling, and disease progression. Importantly, we highlight AM state-specific regulation as a potential therapeutic strategy. Understanding AM heterogeneity as a dynamic process of functional adaptation may provide a new framework for elucidating immune mechanisms in PH and developing more precise therapeutic approaches.

PMID:
42861776
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.

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