{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:14:14Z","timestamp":1791278054783,"version":"4.1.0"},"reference-count":23,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Ferroptosis is a mode of cell death that occurs in myocardial infarction (MI). Signals emanating from apoptotic cells are able to induce macrophage polarization through exosome-loading cargos, which plays a vital role in the process of disease. However, whether ferroptotic cardiomyocytes derived exosome (MI-Exo) during MI act on macrophage polarization and its mechanism remain unclear. In this study, a MI mouse model was established, and cardiac function evaluation and pathological staining were performed. The effect of MI-Exo on polarization of RAW264.7 cells was assessed by the expression of IL-10 and NOS2. Ferroptosis inhibitor of ferrostatin-1 was used to verify whether MI-Exo function was dependents on ferroptosis. Cardiac function and myocardial histomorphology were markedly impaired and massive immune cell infiltration in MI mice, compared with the sham group. The significantly increased MDA content and Fe\n                    <jats:sup>2+<\/jats:sup>\n                    accumulation in the heart tissue of MI mice suggested cardiomyocyte ferroptosis. Compared with the sham group, the expression of M1 marker NOS2 was significantly up-regulated and M2 marker IL-10 was significantly down-regulated in the heart tissue of MI mice. Exosome-derived from MI HL-1 cell-treated with ferrostatin-1 (Fer-1-Exo) and MI-Exo were internalized by RAW 264.7 cells. Compared with culture alone, co-cultured with MI-Exo significantly promoted NOS2 expression and suppressed IL-10 expression, and decreased proportion of Arginase-1-labeled M2 macrophages, also inhibited phagocytosis of RAW 264.7 cells. Wnt1 and \u03b2-cantenin expression also elevated after treated with MI-Exo. However, co-cultured with Fer-1-Exo significantly reversed the above changes on RAW 264.7 cells induced by MI-Exo. In conclusion, ferroptotic cardiomyocytes-derived exosome crosstalk macrophage to induce M1 polarization via Wnt\/\u03b2-cantenin pathway, resulting in pathological progress in MI. This understanding provides novel therapeutic target for MI.\n                  <\/jats:p>","DOI":"10.7717\/peerj.13717","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T03:36:07Z","timestamp":1657078567000},"page":"e13717","source":"Crossref","is-referenced-by-count":50,"title":["Ferroptotic cardiomyocyte-derived exosomes promote cardiac macrophage M1 polarization during myocardial infarction"],"prefix":"10.7717","volume":"10","author":[{"given":"Shengjia","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Wu","sequence":"additional","affiliation":[{"name":"Nursing Department, Huashan Hospital, Fudan University, Shanghai, 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