{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:10:37Z","timestamp":1783296637538,"version":"3.54.6"},"reference-count":26,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation of the Capital Institute of Pediatrics","award":["CXYJ-2021-02"],"award-info":[{"award-number":["CXYJ-2021-02"]}]},{"name":"Research Foundation of the Capital Institute of Pediatrics","award":["82171652"],"award-info":[{"award-number":["82171652"]}]},{"name":"Research Foundation of the Capital Institute of Pediatrics","award":["7232008"],"award-info":[{"award-number":["7232008"]}]},{"name":"Research Foundation of the Capital Institute of Pediatrics","award":["7222017"],"award-info":[{"award-number":["7222017"]}]},{"name":"National Natural Science Foundation of China","award":["CXYJ-2021-02"],"award-info":[{"award-number":["CXYJ-2021-02"]}]},{"name":"National Natural Science Foundation of China","award":["82171652"],"award-info":[{"award-number":["82171652"]}]},{"name":"National Natural Science Foundation of China","award":["7232008"],"award-info":[{"award-number":["7232008"]}]},{"name":"National Natural Science Foundation of China","award":["7222017"],"award-info":[{"award-number":["7222017"]}]},{"name":"Beijing Natural Science Foundation","award":["CXYJ-2021-02"],"award-info":[{"award-number":["CXYJ-2021-02"]}]},{"name":"Beijing Natural Science Foundation","award":["82171652"],"award-info":[{"award-number":["82171652"]}]},{"name":"Beijing Natural Science Foundation","award":["7232008"],"award-info":[{"award-number":["7232008"]}]},{"name":"Beijing Natural Science Foundation","award":["7222017"],"award-info":[{"award-number":["7222017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aims to explore the pathogenic mechanism of H-type hypertension. A rat model of H-type hypertension was established through high-methionine dietary intervention, with subsequent folic acid administration. Untargeted serum metabolomic profiling identified a significant reduction in arachidonic acid (AA) levels in the methionine-enriched group, which were effectively normalized following folic acid supplementation. Transcriptomic analysis revealed methionine-induced upregulation of AA pathway-associated genes Cyp1a1 and Gpr75. In contrast, after the intervention with folic acid, a downregulation of these genes was observed. These findings were corroborated through Western blotting and RT-qPCR validation. In vitro studies using EA.hy926 endothelial cells demonstrated that methionine exposure significantly elevated CYP1A1 expression. Furthermore, methionine stimulation induced marked upregulation of GPR75 and its downstream signaling components (NRAS, MEK1, and ERK1). Population-level evidence from the U.S. NHANES database substantiated significant correlations between essential fatty acids (AA, LA, and GLA) and H-type hypertension prevalence. Our research findings suggest that the CYP1A1\/20-HETE\/GPR75 axis-mediated dysregulation of AA metabolism may be one of the key pathological mechanisms of H-type hypertension. The research results provide clues for the discovery of new therapeutic targets for H-type hypertension.<\/jats:p>","DOI":"10.3390\/ijms26135947","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T11:23:24Z","timestamp":1750418604000},"page":"5947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CYP1A1\/20-HETE\/GPR75 Axis-Mediated Arachidonic Acid Metabolism Dysregulation in H-Type Hypertension Pathogenesis"],"prefix":"10.3390","volume":"26","author":[{"given":"Hangyu","family":"Lv","sequence":"first","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Children\u2019s Medical Center, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Children\u2019s Medical Center, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoling","family":"Bai","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Children\u2019s Medical Center, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Children\u2019s Medical Center, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Children\u2019s Medical Center, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Hyperhomocysteinemia and cardiovascular diseases","volume":"80","author":"Guieu","year":"2022","journal-title":"Ann. 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