{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:22:33Z","timestamp":1785460953040,"version":"3.56.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"High-Level Talent Funding Project of Quanzhou, China","award":["2020C001R"],"award-info":[{"award-number":["2020C001R"]}]},{"name":"the Natural Science Foundation of Xiamen, China","award":["3502Z20227338"],"award-info":[{"award-number":["3502Z20227338"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>This study aimed to investigate the potential compensatory role of plasma exosomal microRNAs (miRNAs), particularly miR-320b, in mitigating early myocardial damage in severe obstructive sleep apnea (OSA) patients without comorbidities. AC16 human cardiomyocytes were co-incubated with plasma exosomes isolated from healthy volunteers (Ctrl-exo) and patients with uncomplicated severe OSA (OSA-exo). Functional assays revealed that OSA-exo significantly enhanced AC16 cell viability, promoted proliferation, and reduced apoptosis. RNA sequencing (RNA-seq) identified 14 myocardial function-related mRNAs in AC16 cardiomyocytes differentially influenced by OSA-exo. Out of the 14 mRNAs, FOXM1, a critical regulator of cardiomyocyte stress response, survival, and regeneration, was verified to be upregulated by OSA-exo by RT-qPCR. Bioinformatic analysis predicted a regulatory relationship between miR-320b and FOXM1, which was confirmed by a dual-luciferase reporter assay. MiR-320b was found to be downregulated in OSA-exo by RT-qPCR. MiR-320b overexpression downregulated FOXM1, induced G0\/G1 cell cycle arrest, reduced cell viability, and increased apoptosis. In a mouse model of chronic intermittent hypoxia (CIH), myocardial FOXM1 exhibited a biphasic expression pattern during disease progression. After 4 weeks of CIH exposure, the mouse myocardium exhibited significantly increased FOXM1 expression and reduced levels of apoptosis compared to control, suggesting an early compensatory response. However, after 12 weeks of CIH exposure, decreased myocardial FOXM1 expression and increased apoptosis were detected, suggesting that the early compensatory protective mechanism was overwhelmed by myocardial injury caused by chronic hypoxia, leading to enhanced cardiomyocyte apoptosis and consequent FOXM1 downregulation. These results suggested that miR-320b downregulation in OSA-exo may serve as a compensatory mechanism to protect against early myocardial injury through the upregulation of FOXM1, highlighting miR-320b and FOXM1 as potential therapeutic targets for OSA-associated cardiomyopathy.<\/jats:p>","DOI":"10.1371\/journal.pone.0332862","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:34:01Z","timestamp":1758908041000},"page":"e0332862","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exosomal miR-320b regulates cardiomyocyte FOXM1 expression and may serve as an early-stage compensatory mechanism in obstructive sleep 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