{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:59:48Z","timestamp":1791910788311,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR\u201022\u20103p is a marker in heart failure. Therefore, miR\u201022\u20103p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real\u2010time polymerase chain reaction detected miR\u201022\u20103p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3\u2010(4,5\u2010dimethyl\u20102\u2010thiazolyl)\u20102,5\u2010diphenyl\u20102\u2010H\u2010tetrazolium bromide (MTT) and PKH26 staining. After overexpressing\/silencing miR\u201022\u20103p in cells, cell viability, apoptosis, and apoptosis\u2010associated markers were detected. Bioinformatic analysis screened the target gene of miR\u201022\u20103p, which was verified by dual\u2010luciferase assay. Regulation of miR\u201022\u20103p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR\u201022\u20103p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR\u201022\u20103p was overexpressed in HF\u2010treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF\u2010treated exosomes were cytotoxic. By regulating apoptosis\u2010related genes, overexpressed miR\u201022\u20103p inhibited cell activity and promoted cell apoptosis. Silenced miR\u201022\u20103p with opposite effects counteracted effects of HF\u2010treated exosomes. FURIN, target gene of miR\u201022\u20103p, was negatively regulated by miR\u201022\u20103p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR\u201022\u20103p in exosomes increases the risk of HF damage.<\/jats:p>","DOI":"10.1111\/cbdd.14142","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T14:08:40Z","timestamp":1662386920000},"page":"550-567","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<scp>MiR<\/scp>\u201022\u20103p in exosomes increases the risk of heart failure after down\u2010regulation of <scp>FURIN<\/scp>"],"prefix":"10.1111","volume":"101","author":[{"given":"Wenlin","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine The First Affiliated Hospital of Soochow University  Suzhou China"},{"name":"Department of Cardiovascular Medicine Wuxi No. 2 People's Hospital  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular 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