{"doi":"10.4049/immunohorizons.2000075","title":"Extracellular miR-146a-5p Induces Cardiac Innate Immune Response and Cardiomyocyte Dysfunction","abstract":"Abstract Previous studies have demonstrated that transient myocardial ischemia leads to release of cellular nucleic acids such as RNA. Extracellular RNA reportedly plays a pivotal role in myocardial inflammation and ischemic injury in animals. RNA profiling has identified that numerous microRNA (miRNAs), such as ss–miR-146a-5p, are upregulated in plasma following myocardial ischemia, and certain uridine-rich miRNAs exhibit strong proinflammatory effects in immune cells via ssRNA-sensing mechanism. However, the effect of extracellular miRNAs on myocardial inflammation and cardiac cell function remains unknown. In this study, we treated adult mouse cardiomyocytes with miR-146a-5p loaded in extracellular vesicles and observed a dose- and TLR7-dependent production of CXCL-2, IL-6, and TNF-α. In vivo, a single dose of myocardial injection of miR-146a-5p induced both cytokine expression (CXCL2, IL-6, and TNF-α) and innate immune cell activation (CD45+ leukocytes, Ly6Cmid+ monocytes, Ly6G+ neutrophils), which was significantly attenuated in the hearts of TLR7 KO mice. We discovered that conditioned media from miR-146a–treated macrophages stimulated proinflammatory cytokine production in adult cardiomyocytes and significantly inhibited their sarcomere shortening. Finally, using an electric cell impedance–sensing assay, we found that the conditioned media from miR-146a–treated cardiac fibroblasts or cardiomyocytes impaired the barrier function of coronary artery endothelial cells. Taken together, these data demonstrate that extracellular miR-146a-5p activates multiple cardiac cells and induces myocardial inflammation and cardiomyocyte dysfunction via intercellular interaction and innate immune TLR7 nucleic acid sensing.","journal":"ImmunoHorizons","year":2020,"id":92209,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"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":461365,"name":"Yang Yang","orcid":"0000-0002-4178-1259","position":1,"is_corresponding":false},{"id":461366,"name":"Jing Zhu","orcid":"0000-0002-8014-2855","position":2,"is_corresponding":false},{"id":461367,"name":"Sheng Wang","orcid":"0000-0002-5625-403X","position":3,"is_corresponding":false},{"id":461368,"name":"Andrew Suen","orcid":"0000-0002-4354-6498","position":4,"is_corresponding":false},{"id":461369,"name":"Stephanie M. Kronstadt","orcid":"0000-0003-0267-6146","position":5,"is_corresponding":false},{"id":461370,"name":"Anjana Jeyaram","orcid":"0000-0002-2181-4367","position":6,"is_corresponding":false},{"id":328545,"name":"Steven M. Jay","orcid":"0000-0002-3827-5988","position":7,"is_corresponding":false},{"id":461371,"name":"Lin Zou","orcid":"0000-0003-0820-4246","position":8,"is_corresponding":false},{"id":461372,"name":"Wei Chao","orcid":"0000-0002-2505-1360","position":9,"is_corresponding":false},{"id":461364,"name":"Briana K. Shimada","orcid":"0000-0003-1521-6966","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:29:54.256205Z","pmid":"32958516","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":[]}