{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:16:34Z","timestamp":1792995394734,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Mitophagy is critically involved in cardiac injury and repair after myocardial infarction (MI), whereas the annexin A family plays an important role in mitophagy. However, the intrinsic molecular underpinnings that orchestrate the homeostasis of mitophagy in the infarcted heart remain to be fully characterized. Here, we aimed to evaluate the role of ANXA2 (annexin A2) in cardiac mitophagy in response to MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Transcriptome analyses were conducted to identify differentially expressed genes and enriched pathways. Mitophagy, mitochondrial function, and cardiac injury and remodeling were analyzed in MI mice and neonatal rat ventricular myocytes with cardiomyocyte-specific\n                      <jats:italic toggle=\"yes\">Anxa2<\/jats:italic>\n                      knockdown or overexpression, as well as in models with\n                      <jats:italic toggle=\"yes\">Anxa2<\/jats:italic>\n                      knockdown combined with\n                      <jats:italic toggle=\"yes\">Phb2<\/jats:italic>\n                      (prohibitin 2) silencing. Immunoprecipitation, mass spectrometry, and glutathione S-transferase pull-down assays were used to identify the interacting proteins of ANXA2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We showed that ANXA2 was highly expressed in murine and human ischemic failing hearts, whereas increased circulating ANXA2 positively correlated with cardiac injury in patients with acute MI. Moreover, cardiomyocyte-specific\n                      <jats:italic toggle=\"yes\">Anxa2<\/jats:italic>\n                      depletion averted cardiac mitophagy inactivation, oxidative stress, cell death, and inflammatory cell infiltration, leading to significant improvements in infarct size, heart function, and cardiac remodeling after MI. Conversely,\n                      <jats:italic toggle=\"yes\">Anxa2<\/jats:italic>\n                      overexpression in cardiomyocytes suppressed mitophagy to exacerbate cardiac injury and deteriorate heart failure after MI. Moreover,\n                      <jats:italic toggle=\"yes\">Anxa2<\/jats:italic>\n                      silencing and overexpression, respectively, in neonatal rat ventricular myocytes under hypoxia in vitro recapitulated the in vivo findings on mitochondrial function and cell death. Mechanistically, we found that ANXA2 directly interacted with the mitophagy receptor PHB2 to competitively block the binding of LC3B (microtubule-associated protein 1 light chain 3 beta) with PHB2 and promote PHB2 proteasomal degradation through K48-linked polyubiquitination mediated by the E3 ligase TRIM29 (tripartite motif-containing 29), resulting in mitophagy inhibition under hypoxia. Consequently,\n                      <jats:italic toggle=\"yes\">Phb2<\/jats:italic>\n                      knockdown abrogated the protective effects of\n                      <jats:italic toggle=\"yes\">Anxa2<\/jats:italic>\n                      deficiency on mitochondrial function, oxidative stress, and cell viability in stressed myocytes in vitro, as well as on heart function and remodeling under MI in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings highlight the significance of ANXA2 inhibition as a molecular brake on mitophagy inactivation in cardiomyocytes under MI and uncover an ANXA2-mediated posttranslational mechanism essential for maintaining mitochondrial homeostasis and alleviating heart failure after MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.077780","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T10:00:13Z","timestamp":1767693613000},"page":"826-844","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of Annexin A2 Facilitates PHB2-Mediated Mitophagy in Cardiomyocytes to Alleviate Cardiac Injury and Remodeling After Infarction"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2406-7456","authenticated-orcid":true,"given":"Ke-Qiong","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."},{"name":"Hubei Provincial Clinical Research Center for Cardiovascular Intervention (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-8676","authenticated-orcid":true,"given":"Zhendong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."},{"name":"Hubei Provincial Clinical Research Center for Cardiovascular Intervention (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-8708","authenticated-orcid":true,"given":"Qiongxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."},{"name":"Hubei Provincial Clinical Research Center for Cardiovascular Intervention (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3426-8630","authenticated-orcid":true,"given":"Huan-Huan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."},{"name":"Hubei Provincial Clinical Research Center for Cardiovascular Intervention (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-0345","authenticated-orcid":true,"given":"Di","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."},{"name":"Hubei Provincial Clinical Research Center for Cardiovascular Intervention (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. Li, Z.L.), Wuhan University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital (K.-Q.D., Z.X., Q.W., H.-H.C., D.F., Q.W., X. 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