{"doi":"10.15252/emmm.201911303","title":"MicroRNA‐483 amelioration of experimental pulmonary hypertension","abstract":"Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses.","journal":"EMBO Molecular Medicine","year":2020,"id":61725,"datarank":1.9113007579451509,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":1.3074980043348783,"self_endowment_contribution":0.6038027536102726,"citer_contribution":1.3074980043348783,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":49,"citers_with_citation_signal":44,"citers_with_endowment":44,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE146774"]},"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":326213,"name":"Yangyang He","orcid":"0000-0002-3517-572X","position":1,"is_corresponding":false},{"id":327638,"name":"Xiaosong Yan","orcid":null,"position":2,"is_corresponding":false},{"id":266294,"name":"Shanshan Chen","orcid":"0000-0001-9723-2403","position":3,"is_corresponding":false},{"id":323530,"name":"Ming He","orcid":"0000-0001-8867-1826","position":4,"is_corresponding":false},{"id":266293,"name":"Yuyang Lei","orcid":"0000-0002-3456-5160","position":5,"is_corresponding":false},{"id":266290,"name":"Jiao Zhang","orcid":"0000-0002-9456-3992","position":6,"is_corresponding":false},{"id":326214,"name":"Brendan Gongol","orcid":"0000-0001-9627-613X","position":7,"is_corresponding":false},{"id":253483,"name":"Mingxia Gu","orcid":"0000-0001-7405-8473","position":8,"is_corresponding":false},{"id":253471,"name":"Yifei Miao","orcid":"0000-0002-8764-1067","position":9,"is_corresponding":false},{"id":326215,"name":"Liang Bai","orcid":"0000-0002-4129-8662","position":10,"is_corresponding":false},{"id":326216,"name":"Xiaopei Cui","orcid":"0000-0002-9724-6175","position":11,"is_corresponding":false},{"id":326217,"name":"Xiaojian Wang","orcid":"0000-0002-1856-8820","position":12,"is_corresponding":false},{"id":326218,"name":"Yixin Zhang","orcid":"0000-0002-1146-8122","position":13,"is_corresponding":false},{"id":326219,"name":"Fenling Fan","orcid":"0000-0002-7732-7701","position":14,"is_corresponding":false},{"id":326220,"name":"Li Zhao","orcid":"0000-0003-0302-1635","position":15,"is_corresponding":false},{"id":326221,"name":"Yuan Li Shen","orcid":"0000-0002-7345-2521","position":16,"is_corresponding":false},{"id":6331,"name":"Chih-Hung Chou","orcid":"0000-0001-5714-1718","position":17,"is_corresponding":false},{"id":308440,"name":"Hsien‐Da Huang","orcid":"0000-0003-2857-7023","position":18,"is_corresponding":false},{"id":270458,"name":"Atul Malhotra","orcid":"0000-0002-9509-1827","position":19,"is_corresponding":false},{"id":240970,"name":"Marlene Rabinovitch","orcid":"0000-0001-7886-7104","position":20,"is_corresponding":false},{"id":326222,"name":"Zhi‐Cheng Jing","orcid":"0000-0003-0493-0929","position":21,"is_corresponding":false},{"id":266299,"name":"John Y.-J. 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