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Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary
Yonghui Li1,2, Haijing Xing1, Yunxing Liu1
1Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.
Abstract:
High-altitude pulmonary hypertension (HAPH) is a debilitating condition caused by chronic hypobaric hypoxia at high altitudes, leading to progressive pulmonary vascular remodeling and right heart failure. The altitude-adapted immune microenvironment plays a pivotal but underappreciated role in HAPH progression: innate immune cells mediate early endothelial damage and proinflammatory signaling, while adaptive immune dysregulation sustains chronic inflammation. This review focuses on hypoxic-induced altitude-adapted immune microenvironment alterations - including immune cell phenotypic reprogramming, metabolic shifts, and spatial reorganization - and their roles in driving endothelial dysfunction, smooth muscle cell proliferation, and fibroblast activation. It also explores immune-cell crosstalk with vascular cells via paracrine signaling/extracellular vesicles, and highlights therapeutic strategies. This article aims to review the roles of hypoxia, inflammation, and oxidative stress in vascular remodeling in HAPH.
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