{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:40:16Z","timestamp":1777887616595,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial ischemia\/reperfusion (I\/R) injury is a major challenge in reperfusion therapy for acute myocardial infarction, primarily due to excessive oxidative stress, inflammation, and cardiomyocyte apoptosis. MicroRNAs are known regulators of cellular stress responses, but the role and underlying mechanism of miR-200a-3p in myocardial I\/R injury remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      , hypoxia\/reoxygenation (H\/R) hypoxia\/reoxygenation (H\/R)-treated human AC16 cardiomyocytes were used to assess the effects of miR-200a-3p modulation on cell viability, apoptosis, oxidative stress, and inflammatory cytokines. The interaction with KEAP1 and downstream NRF2 activation was examined using luciferase assays and protein analyses.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , cardiac-specific AAV9-mediated miR-200a-3p overexpression in mice subjected to I\/R injury was evaluated for myocardial injury, oxidative stress, inflammation, apoptosis, and KEAP1\u2013NRF2 signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MiR-200a-3p was markedly downregulated in H\/R-treated cardiomyocytes and in mouse hearts after I\/R injury. Restoring miR-200a-3p enhanced cell viability, reduced apoptosis, ROS accumulation, lipid peroxidation, and inflammatory cytokine release, and restored antioxidant defenses\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                      <jats:italic>In vivo<\/jats:italic>\n                      , cardiac-specific miR-200a-3p overexpression attenuated myocardial injury, oxidative stress, inflammation, and cardiomyocyte apoptosis. Mechanistically, miR-200a-3p directly targeted KEAP1, promoted NRF2 nuclear translocation, and upregulated downstream antioxidant enzymes including HO-1 and NQO1, with KEAP1 suppression required for its cardioprotective effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that miR-200a-3p protects against myocardial I\/R injury by targeting KEAP1 and activating NRF2-dependent antioxidant signaling, identifying a novel redox-regulatory axis with therapeutic potential, with beneficial effects on myocardial injury and its associated functional impairment.<\/jats:p>\n                  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