Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review

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.