{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:06:38Z","timestamp":1785409598895,"version":"3.56.0"},"reference-count":56,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"crossref","award":["24A0202L1 RS-2025-00553572"],"award-info":[{"award-number":["24A0202L1 RS-2025-00553572"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extracellular vesicles (EVs) hold great potential to deliver microRNAs (miRNAs) in vivo; however, its preferential hepatic accumulation after systemic administration hinders the therapeutic efficacy of miRNAs. Inter-organ communication via endocrine factors is crucial for maintaining physiological homeostasis. Herein, the present study leveraged liver\u2013heart crosstalk to overcome the hepatic tropism of EVs and reframe it as a therapeutic advantage for cardiac injury. In a mouse model of angiotensin II (Ang II)-induced cardiac injury, liver tissues showed distinct changes in inflammation-related proteins compared with saline-treated controls, indicating hepatic involvement in cardiac injury. To establish a liver\u2013heart crosstalk-based therapeutic approach, EV@miR-155 were prepared by loading miRNA-155 into mesenchymal stem cell-derived EVs. After intravenous administration, EV@miR-155 predominantly accumulated in the liver, increased hepatic miRNA-155 levels, and remodeled the hepatic microenvironment. This remodeling suppressed PPAR\u03b1-mediated production of fibroblast growth factor 21, a hepatokine implicated in cardiac pathophysiology, thereby establishing a liver\u2013heart crosstalk axis. Remarkably, EV@miR-155 treatment significantly improved cardiac function and reduced myocardial fibrosis and hypertrophy without inducing systemic toxicity (P&amp;lt;0.05). Therefore, the present study provides a conceptual shift by transforming the natural hepatic tropism of EVs\u2014traditionally regarded as a delivery limitation\u2014into a therapeutic route that enables liver\u2013heart crosstalk-mediated cardiac repair.<\/jats:p>","DOI":"10.1042\/cs20250919","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:31:56Z","timestamp":1783956716000},"page":"1761-1777","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing liver\u2013heart crosstalk via extracellular vesicle-mediated hepatic delivery of microRNAs for cardiac repair"],"prefix":"10.1042","volume":"140","author":[{"given":"Ji-Young","family":"Kang","sequence":"first","affiliation":[{"name":"1Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasom","family":"Mun","sequence":"additional","affiliation":[{"name":"1Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeongseo","family":"Yoo","sequence":"additional","affiliation":[{"name":"2Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgeum","family":"Park","sequence":"additional","affiliation":[{"name":"1Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoong","family":"Lee","sequence":"additional","affiliation":[{"name":"1Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyong","family":"Chung","sequence":"additional","affiliation":[{"name":"1Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuri","family":"Yun","sequence":"additional","affiliation":[{"name":"3GNTPharma Science and Technology Center for Health, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-7225","authenticated-orcid":false,"given":"Boyoung","family":"Joung","sequence":"additional","affiliation":[{"name":"1Division of Cardiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"},{"name":"2Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026073006315352100_B1","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1161\/CIRCRESAHA.121.318005","article-title":"Immune cells and immunotherapy for cardiac injury and repair","volume":"128","author":"Rurik","year":"2021","journal-title":"Circ. 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