{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T13:33:41Z","timestamp":1793972021885,"version":"4.8.0"},"reference-count":72,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK121978"],"award-info":[{"award-number":["1R01DK121978"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK129735"],"award-info":[{"award-number":["1R01DK129735"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK147153"],"award-info":[{"award-number":["1R01DK147153"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty of Medicine, University of Kiel"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cardiorenal syndrome type 1 (CRS1), defined as acute kidney injury occurring in the setting of acute cardiac illness, is associated with substantial morbidity and mortality. Our objective was to determine whether extracellular vesicles (EVs) derived from the injured heart localize to the kidneys and contribute to renal injury in CRS1 and to elucidate the mechanisms by which cardiac-derived EVs mediate kidney damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Using cardiomyocyte-specific EV reporter mice, we characterized the release of cardiac-derived EVs and their biodistribution to the kidneys. Acute myocardial infarction increased circulating levels of these EVs and enhanced their uptake by proximal tubular epithelial cells. To directly assess their impact on the kidney, EVs derived from cardiomyocytes cultured under normoxic (N-EV) or hypoxic (H-EV) conditions were injected into the renal arteries of wild-type mice. H-EV, but not N-EV, induced proximal tubular epithelial cell injury and worsening of kidney function. To identify EV biomarkers, we performed proteomic profiling of cargo from N-EV and H-EV and validated the muscle-specific protein TRIM72 as a biomarker of EVs originating from injured cardiomyocytes. In a porcine CRS1 model, plasma levels of TRIM72-positive EVs were increased, and we demonstrate their delivery to the kidney. Similarly, in CRS1 patients, higher plasma levels of TRIM72-positive EVs correlated with the development of acute kidney injury. Mechanistically, uptake of H-EVs by proximal tubular epithelial cells induced transcription of lipogenic genes and caused lipid accumulation, whereas lipogenesis blockade protected these cells from H-EV-induced injury. We subsequently found that reduced expression of the transcription factor Forkhead Box O3 (FOXO3) drove H-EV-induced transcriptomic reprogramming. H-EV cargo was enriched with specific Foxo3-targeting miRNAs, whose delivery promoted proximal tubular epithelial cell cytotoxicity and oxidative stress, and suppressed FOXO3 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, this work demonstrates that a Foxo3-targeting miRNA heart-to-kidney signal mediated by injured cardiac-derived EVs contributes to kidney injury in CRS1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag230","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:11:06Z","timestamp":1791612666000},"source":"Crossref","is-referenced-by-count":1,"title":["Heart-to-kidney signal by extracellular vesicles promotes kidney injury in cardiorenal syndrome"],"prefix":"10.1093","author":[{"given":"Morad","family":"Asadi","sequence":"first","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, Annenberg Building room 23-68D, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos G","family":"Santos-Gallego","sequence":"additional","affiliation":[{"name":"Cardiology Department, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Anastasiadou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, Annenberg Building room 23-68D, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob Christoph","family":"Voran","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III (Cardiology and Angiology), University Hospital Schleswig-Holstein , Arnold-Heller-Str. 3, Kiel ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research, Partner Site Hamburg\/Kiel\/L\u00fcbeck , Arnold-Heller-Str. 3, Kiel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt-Johannes","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III (Cardiology and Angiology), University Hospital Schleswig-Holstein , Arnold-Heller-Str. 3, Kiel ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research, Partner Site Hamburg\/Kiel\/L\u00fcbeck , Arnold-Heller-Str. 3, Kiel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter W","family":"Korsmo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, Annenberg Building room 23-68D, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, Annenberg Building room 23-68D, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Requena-Ibanez","sequence":"additional","affiliation":[{"name":"Cardiology Department, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Fardman","sequence":"additional","affiliation":[{"name":"Cardiology Department, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasile","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, Annenberg Building room 23-68D, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yansui","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place, Annenberg Building room 23-68D, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2488-8510","authenticated-orcid":false,"given":"Gohar","family":"Mosoyan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai , One Gustave L. 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