Exosomes are nanoscale extracellular vesicles that are released from the cell by exocytosis, they transport diverse bioactive cargo, including proteins, lipids, nucleic acids like Deoxyriboynucleic acid (DNA) and ribonucleic acid (RNA), and mitochondria, thereby serving as key mediators of intercellular communication. Although exosome abundance is elevated in pulmonary hypertension (PH), whether exosomes released from hypertensive lungs transmit functional mitochondria and how their protein cargo is remodeled in disease remain unresolved. Here, we characterized exosomes isolated from blood drained from the left ventricle of rats with Sugen5416/hypoxia (SU/Hx)–induced PH compared with Sugen5416/normoxia (SU/Nx) controls. Unbiased proteomic profiling revealed exosomal proteins spanning coagulation, complement and immune pathways, metabolic processes, receptor signaling, and cytoskeletal structure. Notably, the majority of proteins were reduced in SU/Hx exosomes; however, select cargos—including attractin, long-chain fatty acid-CoA ligase 1, vascular cell adhesion molecule-1, and Ig-gamma-2A chain C region—were significantly enriched. Several proteases, antioxidants, and signaling molecules relevant to vascular and lung function exhibited disease-associated post-translational modifications. Flow-cytometric analysis further demonstrated a higher abundance of functionally active mitochondria in SU/Hx exosomes relative to controls. Collectively, these findings provide, to our knowledge, the first evidence that exosomes originating from hypertensive lungs deliver functional mitochondria and a remodeled protein landscape with the potential to influence vascular and organ homeostasis in recipient cells. These results highlight a previously unrecognized mechanism of pathological signaling in pulmonary hypertension proposing that a profound study would help identify disease-altered exosomal cargo as a potential therapeutic and diagnostic target. Funding source: RO1HL166546 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
D’silva et al. (Fri,) studied this question.