{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:51:38Z","timestamp":1793328698616,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007772","name":"Agir pour les Maladies Chroniques","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003100","name":"F\u00e9d\u00e9ration Fran\u00e7aise de Cardiologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003100","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>\n                    Chronic intermittent hypoxia (IH), a major feature of obstructive sleep apnea syndrome (OSA), is associated with greater severity of myocardial infarction. In this study, we performed RNA sequencing of cardiac samples from mice exposed to IH, which reveals a specific transcriptomic signature of the disease, relative to mitochondrial remodeling and cell death. Corresponding to its activation under chronic IH, we stabilized the Hypoxia Inducible Factor\u20101\u03b1 (HIF\u20101\u03b1) in cardiac cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and observed its association with an increased autophagic flux. In accordance, IH induced autophagy and mitophagy, which are decreased in HIF\u20101\u03b1\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice compared to wild\u2010type animals, suggesting that HIF\u20101 plays a significant role in IH\u2010induced mitochondrial remodeling. Next, we showed that the AMPK metabolic sensor, typically activated by mitochondrial stress, is inhibited after 3\u2009weeks of IH in hearts. Therefore, we assessed the effect of metformin, an anti\u2010diabetic drug and potent activator of AMPK, on myocardial response to ischemia\u2013reperfusion (I\/R) injury. Daily administration of metformin significantly decreases infarct size without any systemic beneficial effect on insulin resistance under IH conditions. The cardioprotective effect of metformin was lost in AMPK\u03b12 knock\u2010out mice, demonstrating that AMPK\u03b12 isoform promotes metformin\u2010induced cardioprotection in mice exposed to IH. Mechanistically, we found that metformin inhibits IH\u2010induced mitophagy in myocardium and decreases HIF\u20101\u03b1 nuclear expression in mice subjected to IH.\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments demonstrated that metformin induced HIF\u20101\u03b1 phosphorylation, decreased its nuclear localization, and HIF\u20101 transcriptional activity. Collectively, these results identify the AMPK\u03b12 metabolic sensor as a novel modulator of HIF\u20101 activity. Our data suggest that metformin could be considered as a cardioprotective drug in OSA patients independently of their metabolic status.\n                  <\/jats:p>","DOI":"10.1111\/febs.70110","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:46:31Z","timestamp":1747190791000},"page":"3942-3959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metformin protects the heart against chronic intermittent hypoxia through\n                    <scp>AMPK<\/scp>\n                    \u2010dependent phosphorylation of\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1"],"prefix":"10.1111","volume":"292","author":[{"given":"Sophie","family":"Moulin","sequence":"first","affiliation":[{"name":"HP2, Universit\u00e9 Grenoble Alpes, INSERM, Laboratory HP2  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