{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:06:16Z","timestamp":1784279176008,"version":"3.55.0"},"reference-count":32,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tianshan Talent Training Program Autonomous Region","award":["2022TSYCLJ0067"],"award-info":[{"award-number":["2022TSYCLJ0067"]}]},{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82460097"],"award-info":[{"award-number":["82460097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82260071"],"award-info":[{"award-number":["82260071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Key Project of Xinjiang Natural Science Foundation","award":["2024D01D22"],"award-info":[{"award-number":["2024D01D22"]}]},{"name":"Key research and development project of Xinjiang Uygur Autonomous Region","award":["2022B03022-4"],"award-info":[{"award-number":["2022B03022-4"]}]},{"name":"The Department of Rehabilitation Medicine at The First Affiliated Hospital of Xinjiang Medical University","award":["2023YFY-QKMS-10"],"award-info":[{"award-number":["2023YFY-QKMS-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammatory infiltration constitutes a fundamental pathophysiological mechanism in myocardial ischemia-reperfusion (IR) injury, characterized by its role in initiating tissue damage, amplifying pathological inflammatory cascades, and exacerbating structural and functional impairment of the myocardium. Integrated transcriptomic and metabolomic analysis identified the metabolite itaconic acid as a potential key regulator in IR injury. Therefore, we assessed the effect of its derivative, 4-octyl itaconate (4-OI), on inflammatory infiltration in a mouse model of IR injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following establishment of a myocardial IR model, tissue samples from the infarct border zone were harvested for transcriptomics and wide-target metabolomic sequencing. Bioinformatics methods were used to analyze the transcriptomics and metabolomics results separately and to perform a joint analysis. Molecular docking and molecular dynamics modeling were employed to explore proteins bound to itaconic acid. Following intragastric administration of 4-OI to myocardial IR mice, echocardiography was performed. Plasma levels of interleukin-4 (IL4), interleukin10 (IL10), cardiac troponin T (cTnT), and creatine kinase-myocardial band (CKMB) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial inflammatory infiltration was evaluated by hematoxylin and eosin Staining (HE staining), while inflammatory marker expression associated with macrophages was evaluated by immunohistochemical staining for inducible nitric oxide synthase (iNOS) and immune responsive gene 1 (IRG1). Macrophage heterogeneity was further assessed by immunofluorescence co-localization staining for F4\/80, CCR2, and CD206. Additionally, mRNA expression levels of Interleukin-1 beta (Il1b), Tumor Necrosis Factor-alpha (Tnfa), Il4, and Il10 in myocardial tissue were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Integrated transcriptomic and metabolomic analysis identified itaconic acid as a potential metabolite modulating myocardial IR injury. Preliminary molecular docking analysis suggested possible\n                      <jats:italic>in silico<\/jats:italic>\n                      interactions between itaconic acid and Pla2g2d, Lcn2, and Gpr55 proteins, which require further experimental validation. A derivative of itaconic acid, 4-OI, significantly ameliorated myocardial IR injury in mice, reduced inflammatory infiltration, decreased iNOS-associated staining, and modestly increased Arg1-associated staining in the infarct border zone. This treatment was also accompanied by differences in macrophage marker-defined populations, reflected by fewer F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      CCR2\n                      <jats:sup>+<\/jats:sup>\n                      and more F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      CD206\n                      <jats:sup>+<\/jats:sup>\n                      cells in the injured myocardium.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.21525","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T08:36:21Z","timestamp":1784277381000},"page":"e21525","source":"Crossref","is-referenced-by-count":0,"title":["Integrated transcriptomic and metabolomic analysis reveals the regulatory role of itaconic acid in inflammatory infiltration during myocardial ischemia-reperfusion injury"],"prefix":"10.7717","volume":"14","author":[{"given":"QuanWei","family":"Pei","sequence":"first","affiliation":[{"name":"Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University,  Urumqi, XinJiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZeXin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University,  Urumqi, XinJiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SiJia","family":"Dong","sequence":"additional","affiliation":[{"name":"Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University,  Urumqi, XinJiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QiQi","family":"Shao","sequence":"additional","affiliation":[{"name":"Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University,  Urumqi, XinJiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhenYan","family":"Fu","sequence":"additional","affiliation":[{"name":"Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University,  Urumqi, XinJiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YiTong","family":"Ma","sequence":"additional","affiliation":[{"name":"Heart Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University,  Urumqi, XinJiang, 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