{"doi":"10.1101/2020.09.09.20191338","title":"TGF-β1 in extracellular vesicles from HIV-infected plasma and macrophages linked to cardiopulmonary dysfunction","abstract":"Abstract Rationale Extracellular vesicles (EVs) have emerged as important mediators in cell-cell communication and disease pathogenesis; however, their relevance in pulmonary hypertension (PH) secondary to HIV infection is yet to be explored. Objective To examine the role of circulating small EVs and monocyte-derived macrophage (MDM) EVs in the development of HIV-associated PH Methods EVs isolated from plasma of HIV-infected drug users and non-users with/without PH and from supernatants of HIV-infected MDMs treated with/without second hit of cocaine were studied for their effect on vascular dysfunction both in vitro and in vivo . Measurements and Main Results We report significantly higher numbers of plasma derived EVs (PEVs) carrying higher levels of TGF-β1 in people living with HIV (PLWH) that had PH compared to non-PH PLWH. Importantly, levels of these TGF-β1 loaded PEVs correlated with pulmonary arterial systolic pressures, CD4 counts, but not with diffusion capacity for carbon monoxide or viral load. Correspondingly, enhanced TGF-β1-dependent pulmonary endothelial injury and smooth muscle hyperplasia was observed. Cocaine treatment of HIV-1 infected-MDMs resulted in increased number of TGF-β1 high-EVs. Intravenous injection of these EVs in rats led to increased right ventricle systolic pressure accompanied with myocardial injury and increased levels of serum endothelin-1, TNF-α, and cardiac Troponin-I. Conversely, pretreatment of rats with TGFβ-Receptor 1 inhibitor prevented these EV-mediated changes. Conclusion Findings define the ability of macrophage-derived small EVs to cause pulmonary vascular modeling and PH via modulation of TGF-β signaling and suggest clinical implications of circulating TGF-β high-EVs as a potential biomarker of HIV-PH.","journal":"medRxiv","year":2020,"id":127360,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":262164,"name":"Stuti Agarwal","orcid":"0000-0002-4436-942X","position":1,"is_corresponding":false},{"id":576069,"name":"Aatish Mahajan","orcid":"0000-0002-5064-6921","position":2,"is_corresponding":false},{"id":576070,"name":"Ashok Kumar","orcid":"0000-0002-2718-7544","position":3,"is_corresponding":false},{"id":262163,"name":"Aradhana Mohan","orcid":"0000-0003-4467-4659","position":4,"is_corresponding":false},{"id":576071,"name":"Ling Chen","orcid":"0000-0002-4595-6028","position":5,"is_corresponding":false},{"id":346891,"name":"Priscilla Y. Hsue","orcid":"0000-0002-3427-6043","position":6,"is_corresponding":false},{"id":487859,"name":"Prabhakar Chalise","orcid":"0000-0001-5581-1220","position":7,"is_corresponding":false},{"id":313765,"name":"Alison Morris","orcid":"0000-0002-7290-6536","position":8,"is_corresponding":false},{"id":262166,"name":"Navneet K. Dhillon","orcid":"0000-0001-6582-5757","position":9,"is_corresponding":false},{"id":299501,"name":"Balaji Krishnamachary","orcid":"0000-0001-6137-5832","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:30.930746Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}