Abstract
Pulmonary hypertension (PH) is a progressive vasculopathy characterized by pulmonary vascular remodeling, right ventricular maladaptation, and premature death. Exosomes, an endosome-derived subset of small extracellular vesicles, mediate intercellular communication through the transfer of selected RNAs, proteins, and lipids. In PH, they can modulate endothelial dysfunction, pulmonary artery smooth muscle cell proliferation and phenotypic switching, immune dysregulation, and right ventricular remodeling, implicating them in key aspects of disease pathobiology. These properties have prompted interest in exosomes as minimally invasive biomarkers and as candidates for cell-free therapeutic delivery. However, clinical translation remains at an early stage. Most evidence supporting exosome-based therapeutic strategies in PH is preclinical, whereas current clinical data are largely limited to exploratory biomarker studies. Important gaps also remain in distinguishing exosomes from other extracellular vesicle populations and in addressing methodological standardization, heterogeneity, cargo attribution, biodistribution, dosing, and clinical validation. This review summarizes current evidence on exosome biology in PH and discusses both translational opportunities and the major barriers to clinical implementation.