{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:14Z","timestamp":1785434894275,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L246058"],"award-info":[{"award-number":["L246058"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007937","name":"Peking University","doi-asserted-by":"publisher","award":["BMU2025YXXLHAIYX024-2025"],"award-info":[{"award-number":["BMU2025YXXLHAIYX024-2025"]}],"id":[{"id":"10.13039\/501100007937","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BMU2025YXXLHAIYX024-2025"],"award-info":[{"award-number":["BMU2025YXXLHAIYX024-2025"]}],"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["CFH2024-2-4083"],"award-info":[{"award-number":["CFH2024-2-4083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>The role of immunoresponsive gene 1 (IRG1)\u2013itaconate (ITA) in hypertension remains poorly understood. This study aimed to investigate this role and the underlying mechanisms. IRG1 expression and ITA levels were assessed by Western blotting, targeted metabolomics, and ELISA. We employed global Irg1 (mouse gene coding IRG1)-knockout mice, smooth muscle cell (SMC)-specific Irg1 overexpression mice, and mice receiving intraperitoneal ITA injection. Hypertension was induced by angiotensin II (Ang II) infusion. Blood pressure was measured by tail-cuff method and radiotelemetry, while vascular structure and function were evaluated by histology, vascular ring assays, and Western blotting. The target proteins of ITA were identified through thermal proteomic profiling, cellular thermal shift assay, surface plasmon resonance, and molecular docking. IRG1 expression and ITA levels were significantly upregulated in mouse aortas and vascular smooth muscle cells (VSMCs) under hypertensive conditions. Irg1 knockout markedly attenuated Ang II-induced hypertension and vascular remodeling, whereas SMC-specific Irg1 overexpression or exogenous ITA exacerbated these pathological phenotypes. Mechanistically, ITA directly bound to cystathionine gamma-lyase (CTH) at cysteine 229, inhibiting its enzymatic activity and hydrogen sulfide (H2S) production. These findings demonstrate that IRG1\u2013ITA promotes hypertension and vascular remodeling by directly targeting CTH and suppressing H2S production, suggesting a novel therapeutic target.<\/jats:p>","DOI":"10.3390\/jcdd13070338","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:27Z","timestamp":1784564367000},"page":"338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunoresponsive Gene 1\u2013Itaconate Exacerbates Hypertension by Inhibiting the Cystathionine Gamma-Lyase\/Hydrogen Sulfide Pathway"],"prefix":"10.3390","volume":"13","author":[{"given":"Minglu","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Cardiology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-2629","authenticated-orcid":false,"given":"Chenyu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Physiology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhou","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Huang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Congenital Heart Disease, Ministry of Education, Institute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-9234","authenticated-orcid":false,"given":"Ling","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China"},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18014","DOI":"10.1038\/nrdp.2018.14","article-title":"Hypertension","volume":"4","author":"Oparil","year":"2018","journal-title":"Nat. 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