{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:48:24Z","timestamp":1781088504755,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T00:00:00Z","timestamp":1694217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Vitamin D receptors (VDR) play important roles in cardiovascular, immune, metabolic and other functions. Activation of VDR may help improve endothelial dysfunction, atherosclerosis, vascular calcification, and cardiac hypertrophy. However, the specific target genes and mechanisms of VDR in improving Human Umbilical Vein Endothelial Cell (HUVEC) functions remain unclear. This study aims to investigate the function and mechanism of VDR in HUVECs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Endothelial dysfunction cell model was constructed by oxidized low\u2010density lipoprotein (ox\u2010LDL). An animal model of atherosclerosis was established in male homozygous Apoe\u2212\/\u2212 mice (6\u2009weeks) on a high fat diet for 6\u2009weeks. The relationship between VDR and adrenomedullin (ADM) was studied by bioinformatics analysis, ChIP, and luciferase reporter gene analysis. Endothelial cell function was evaluated by Transwell migration and Tube Formation tests. Ferroptosis was detected by measuring intracellular iron content, levels of oxidative stress markers, and ferroptosis related proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overexpression of VDR in HUVECs inhibits ox\u2010LDL\u2010induced endothelial dysfunction and ferroptosis. VDR binds to the ADM promoter sequence and regulates the transcription of ADM. Inhibition of ADM promotes ox\u2010LDL\u2010induced endothelial dysfunction and ferroptosis. ADM regulates ox\u2010LDL\u2010induced endothelial dysfunction and ferroptosis through the AMPK signaling pathway. Overexpression of VDR in Apoe\u2212\/\u2212 mice inhibited lipid deposition and plaque area in atherosclerotic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>VDR inhibits ox\u2010LDL\u2010induced endothelial dysfunction and ferroptosis by regulating ADM transcription and acting on AMPK signaling pathway. Overexpression of VDR in Apoe\u2212\/\u2212 mice reduced lipid deposition and plaque area in the thoracic aorta of atherosclerotic mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tox.23958","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T17:10:01Z","timestamp":1694279401000},"page":"199-211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>Adrenomedullin<\/scp>, transcriptionally regulated by <scp>vitamin D receptors<\/scp>, alleviates atherosclerosis in mice through suppressing <scp>AMPK<\/scp>\u2010mediated endothelial ferroptosis"],"prefix":"10.1002","volume":"39","author":[{"given":"Yanchao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine The Second Affiliated Hospital of Xi'an Jiaotong University  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