{"doi":"10.1161/circresaha.119.316398","title":"Long Range Endocrine Delivery of Circulating miR-210 to Endothelium Promotes Pulmonary Hypertension","abstract":"Rationale: Unproven theories abound regarding the long-range uptake and endocrine activity of extracellular blood-borne microRNAs into tissue. In pulmonary hypertension (PH), microRNA-210 (miR-210) in pulmonary endothelial cells promotes disease, but its activity as an extracellular molecule is incompletely defined. Objective: We investigated whether chronic and endogenous endocrine delivery of extracellular miR-210 to pulmonary vascular endothelial cells promotes PH. Methods and Results: Using miR-210 replete (wild-type [WT]) and knockout mice, we tracked blood-borne miR-210 using bone marrow transplantation and parabiosis (conjoining of circulatory systems). With bone marrow transplantation, circulating miR-210 was derived predominantly from bone marrow. Via parabiosis during chronic hypoxia to induce miR-210 production and PH, miR-210 was undetectable in knockout-knockout mice pairs. However, in plasma and lung endothelium, but not smooth muscle or adventitia, miR-210 was observed in knockout mice of WT-knockout pairs. This was accompanied by downregulation of miR-210 targets ISCU (iron-sulfur assembly proteins)1/2 and COX10 (cytochrome c oxidase assembly protein-10), indicating endothelial import of functional miR-210. Via hemodynamic and histological indices, knockout-knockout pairs were protected from PH, whereas knockout mice in WT-knockout pairs developed PH. In particular, pulmonary vascular engraftment of miR-210–positive interstitial lung macrophages was observed in knockout mice of WT-knockout pairs. To address whether engrafted miR-210–positive myeloid or lymphoid cells contribute to paracrine miR-210 delivery, we studied miR-210 knockout mice parabiosed with miR-210 WT; Cx3cr1 knockout mice (deficient in myeloid recruitment) or miR-210 WT; Rag1 knockout mice (deficient in lymphocytes). In both pairs, miR-210 knockout mice still displayed miR-210 delivery and PH, thus demonstrating a pathogenic endocrine delivery of extracellular miR-210. Conclusions: Endogenous blood-borne transport of miR-210 into pulmonary vascular endothelial cells promotes PH, offering fundamental insight into the systemic physiology of microRNA activity. These results also describe a platform for RNA-mediated crosstalk in PH, providing an impetus for developing blood-based miR-210 technologies for diagnosis and therapy in this disease.","journal":"Circulation Research","year":2020,"id":94260,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":394723,"name":"Jonathan Florentin","orcid":"0000-0001-7481-4128","position":1,"is_corresponding":false},{"id":430554,"name":"Yi‐Yin Tai","orcid":"0000-0003-3674-0783","position":2,"is_corresponding":false},{"id":469764,"name":"Stéphanie Torrino","orcid":"0000-0002-8280-5907","position":3,"is_corresponding":false},{"id":470629,"name":"Lee Ohayon","orcid":null,"position":4,"is_corresponding":false},{"id":369007,"name":"Tomasz Brzóska","orcid":"0000-0002-7431-3590","position":5,"is_corresponding":false},{"id":430553,"name":"Ying Tang","orcid":"0000-0002-2532-3477","position":6,"is_corresponding":false},{"id":470630,"name":"Jimin Yang","orcid":null,"position":7,"is_corresponding":false},{"id":469765,"name":"Vinny Negi","orcid":"0000-0003-3120-6952","position":8,"is_corresponding":false},{"id":470631,"name":"Chen-­Shan Chen Woodcock","orcid":null,"position":9,"is_corresponding":false},{"id":339994,"name":"Michael G. Risbano","orcid":"0000-0003-3334-7046","position":10,"is_corresponding":false},{"id":431407,"name":"Seyed Mehdi Nouraie","orcid":null,"position":11,"is_corresponding":false},{"id":369012,"name":"Prithu Sundd","orcid":"0000-0001-7568-5719","position":12,"is_corresponding":false},{"id":469766,"name":"Thomas Bertero","orcid":"0000-0002-4801-9902","position":13,"is_corresponding":false},{"id":310365,"name":"Partha Dutta","orcid":"0000-0001-7456-1757","position":14,"is_corresponding":false},{"id":270567,"name":"Stephen Y. Chan","orcid":"0000-0002-9520-7527","position":15,"is_corresponding":false},{"id":431402,"name":"Jingsi Zhao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T22:32:04.778261Z","pmid":"32493166","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":[]}