{"doi":"10.1111/jvim.15762","title":"Extracellular vesicular microRNAs as potential biomarker for early detection of doxorubicin-induced cardiotoxicity","abstract":"BACKGROUND: Long-term use of doxorubicin (DOX) is limited by cumulative dose-dependent cardiotoxicity. OBJECTIVES: Identify plasma extracellular vesicle (EV)-associated microRNAs (miRNAs) as a biomarker for cardiotoxicity in dogs by correlating changes with cardiac troponin I (cTnI) concentrations and, echocardiographic and histologic findings. ANIMALS: Prospective study of 9 client-owned dogs diagnosed with sarcoma and receiving DOX single-agent chemotherapy (total of 5 DOX treatments). Dogs with clinically relevant metastatic disease, preexisting heart disease, or breeds predisposed to cardiomyopathy were excluded. METHODS: Serum concentration of cTnI was monitored before each treatment and 1 month after the treatment completion. Echocardiography was performed before treatments 1, 3, 5, and 1 month after completion. The EV-miRNA was isolated and sequenced before treatments 1 and 3, and 1 month after completion. RESULTS: Linear mixed model analysis for repeated measurements was used to evaluate the effect of DOX. The miR-107 (P = .03) and miR-146a (P = .02) were significantly downregulated whereas miR-502 (P = .02) was upregulated. Changes in miR-502 were significant before administration of the third chemotherapeutic dose. When stratifying miRNA expression for change in left ventricular ejection fraction, upregulation of miR-181d was noted (P = .01). Serum concentration of cTnI changed significantly but only 1 month after treatment completion, and concentrations correlated with left ventricular ejection fraction and left ventricular internal dimension in diastole. CONCLUSION AND CLINICAL SIGNIFICANCE: Downregulation of miR-502 was detected before significant changes in cTnI concentrations or echocardiographic parameters. Further validation using a larger sample size will be required.","journal":"Journal of Veterinary Internal Medicine","year":2020,"id":92791,"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":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"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":463834,"name":"Sally R. Robinson","orcid":"0000-0003-4711-1667","position":1,"is_corresponding":false},{"id":463835,"name":"Nicholas A. Robinson","orcid":"0000-0001-5745-5047","position":2,"is_corresponding":false},{"id":464694,"name":"Katherine E. Lopez","orcid":null,"position":3,"is_corresponding":false},{"id":464695,"name":"Dawn M. Meola","orcid":null,"position":4,"is_corresponding":false},{"id":464696,"name":"Lisa G. Barber","orcid":null,"position":5,"is_corresponding":false},{"id":464697,"name":"Barret J. Bulmer","orcid":null,"position":6,"is_corresponding":false},{"id":464698,"name":"Jerome Calvalido","orcid":null,"position":7,"is_corresponding":false},{"id":349957,"name":"John E. Rush","orcid":"0000-0002-8277-8996","position":8,"is_corresponding":false},{"id":253232,"name":"Ashish Yeri","orcid":null,"position":9,"is_corresponding":false},{"id":251878,"name":"Saumya Das","orcid":"0000-0002-4521-4606","position":10,"is_corresponding":false},{"id":349960,"name":"Vicky K. Yang","orcid":"0000-0002-1281-4250","position":11,"is_corresponding":false},{"id":464693,"name":"Amelie Beaumier","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T22:30:31.563852Z","pmid":"32255536","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":[]}