{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:46:18Z","timestamp":1785818778756,"version":"3.56.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute myocardial infarction (AMI), characterized by acute myocardial necrosis due to coronary occlusion, is a life-threatening cardiovascular event. Ferroptosis critically contributes to ischemic injury, yet its causal regulators in AMI, particularly in endothelial cells, remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated AMI transcriptomics with summary-data-based Mendelian randomization (SMR) and colocalization to identify causal ferroptosis-related transcription factor (TF). A miRNA-TF-mRNA regulatory network was constructed via miRNA-TF and TF-target prediction. Subsequent analyses, including TF binding site prediction, GSEA, GeneMANIA, gene-disease and gene-drug association screening, phenome-wide association study (PheWAS), ROC curve evaluation, and RT-qPCR validation in HUVECs, were performed to characterize the molecular mechanisms of this axis in AMI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      EPAS1 was identified as a causal ferroptosis-related TF in AMI (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>SMR<\/jats:sub>\n                      &amp;lt; 0.05;\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>HEIDI<\/jats:sub>\n                      &amp;gt; 0.05). We constructed a ferroptosis-related miRNA-TF-mRNA network and identified a novel endothelial-specific axis, hsa-miR-138-5p\/EPAS1\/BACH1. RT-qPCR in HUVECs validated the GEO-derived expression patterns of axis components. PheWAS further revealed no significant adverse phenotypic associations for genes within this axis, supporting the druggability of approved compounds targeting it.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies EPAS1 as a TF with suggestive genetic links to AMI risk and characterizes a novel endothelial-enriched hsa-miR-138-5p\/EPAS1\/BACH1 regulatory axis governing ferroptosis. This molecular cascade provides candidate molecular clues for subsequent preclinical research into cardioprotective strategies targeting ferroptosis in AMI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1893164","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:26:55Z","timestamp":1785817615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial EPAS1 as a prognostic and therapeutic target in acute myocardial infarction: integrative bioinformatics, Mendelian randomization and experimental validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaona","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, Yunnan, 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Cardiology, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najie","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, Yunnan, 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