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DCM is characterized by left ventricular diastolic dysfunction, hypertrophy, and fibrosis, with impaired myocardial angiogenesis contributing to adverse cardiovascular outcomes. Despite this, targeted therapies for angiogenesis restoration in DCM remain elusive. Through bioinformatic analysis of public databases, we identified egl-9 family hypoxia inducible factor 1 (<jats:italic>EGLN1<\/jats:italic>) as a differentially expressed gene in both preclinical DCM models and clinical specimens. To validate its role, we established mice model of diabetes and corresponding endothelial cells cultures under hyperglycemic conditions. Results demonstrated significant upregulation of EGLN1 in diabetic mice, correlating with angiogenesis impairment. Intriguingly, EGLN1 inhibition attenuated high glucose-induced endothelial dysfunction by activating autophagy pathways, as evidenced by increased LC3-II\/LC3-I ratios and decreased P62 levels. These findings unveil EGLN1 as a novel regulator of myocardial angiogenesis in DCM, proposing autophagy activation as a potential therapeutic strategy to ameliorate diabetic cardiovascular complications. This study provides the first evidence linking EGLN1 dysregulation to angiogenesis defects in DCM, offering insights for targeted intervention development.<\/jats:p>","DOI":"10.1038\/s41598-025-19745-6","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:43:33Z","timestamp":1760453013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["EGLN1 inhibition reverses angiogenesis impairment in hyperglycemia by activating autophagy"],"prefix":"10.1038","volume":"15","author":[{"given":"Fengli","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"19745_CR1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12933-024-02239-6","volume":"23","author":"HJ Sun","year":"2024","unstructured":"Sun, H. 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