{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:08:23Z","timestamp":1791544103988,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170274"],"award-info":[{"award-number":["82170274"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470418"],"award-info":[{"award-number":["82470418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200447"],"award-info":[{"award-number":["82200447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470476"],"award-info":[{"award-number":["82470476"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304477"],"award-info":[{"award-number":["82304477"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515011747"],"award-info":[{"award-number":["2022A1515011747"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013074"],"award-info":[{"award-number":["2024A1515013074"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Atherosclerosis (AS) is a major cause of cardiovascular diseases, driven by chronic inflammation and macrophage polarization toward a proinflammatory phenotype. Pyruvate carboxylase (PC), a mitochondrial enzyme involved in glucose metabolism, is implicated in various metabolic disorders; however, its role in AS remains unclear. This study aims to investigate the role and mechanism of PC on macrophages in AS. PC is upregulated in macrophages of humans and mice with AS. Myeloid cell\u2010specific PC knockout mice are generated to investigate the effects of PC deletion on atherosclerotic plaque formation. Myeloid cell\u2010specific PC deficiency mitigates high\u2010fat diet\u2010induced\u00a0atherosclerotic lesions in apolipoprotein E knockout mice and mice injected with adeno\u2010associated virus\u2010\n                    <jats:italic>\n                      PCSK9\n                      <jats:sup>DY<\/jats:sup>\n                    <\/jats:italic>\n                    . PC deletion enhances mitochondrial respiration and reduces glycolytic activity, thereby reducing reactive oxygen species overproduction and mitochondrial damage in macrophages. PC activates the hypoxia\u2010inducible factor\u20101 (HIF\u20101) signaling pathway through macrophage metabolic reprogramming. PC induces nuclear translocation of HIF\u20101\u03b1 in atherosclerotic aortic roots by preventing HIF\u20101\u03b1 from proteasome degradation. HIF\u20101\u03b1 stabilizer reverses the anti\u2010inflammatory effect of macrophage\u2010PC ablation in atherogenesis; however, inhibiting HIF\u20101\u03b1 suppresses the proinflammatory macrophage phenotype induced by PC overexpression. This study indicates that macrophage PC aggravates AS through macrophage metabolic reprogramming, promoting inflammatory responses in macrophages through the HIF\u20101 signaling pathway.\n                  <\/jats:p>","DOI":"10.1002\/advs.202417128","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T07:38:02Z","timestamp":1747726682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia\u2010Inducible Factor\u20101 Signaling Pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Ling\u2010Na","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran\u2010Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Ru","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao\u2010Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics General Hospital of Southern Theater Command of PLA The First School of Clinical Medicine Southern Medical University  Guangzhou 510010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Le","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"},{"name":"Department of Cardiovascular Surgery Zhujiang Hospital Southern Medical University  Guangzhou 510280 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De\u2010Shen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"},{"name":"Laboratory of Cardiovascular Science Beijing Clinical Research Institute Beijing Friendship Hospital Capital Medical University  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Xia","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin\u2010Bao","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China  Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Xiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics Guangzhou Women and Children's Medical Centre Guangzhou Medical University  Guangzhou 511400 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Ping","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao\u2010Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-1177","authenticated-orcid":false,"given":"Fang\u2010Ze","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.010"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312802"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.15.9.1512"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.09.010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0902.104353"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.016"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0291-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103123"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.064"},{"key":"e_1_2_9_11_1","volume":"114","author":"Choi P. H.","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118803"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI72873","volume":"125","author":"Sellers K.","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.03.014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.06.008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00480-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab660"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2023.11.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181341498"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-314427"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.04.009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0cs00203h"},{"key":"e_1_2_9_23_1","first-page":"136","volume":"119","author":"Park Y. M.","year":"2009","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000229218.97976.43"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13668-3"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae248"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2370379"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2956"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13280"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.06.008"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302153"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315833"},{"key":"e_1_2_9_34_1","first-page":"120","volume":"36","author":"Choi K. S.","year":"2003","journal-title":"J. Biochem. Mol. Biol."},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22642"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.09.003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0096-z"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00761-w"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M901790200"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313290"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307830"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0299-0"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.88223"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42634-3"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1144"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202487200"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048952"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0610292"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.06.018"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84431"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.305551"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-023-01840-x"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103229"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202417128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202417128","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202417128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:09:05Z","timestamp":1770833345000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202417128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":54,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/advs.202417128"],"URL":"https:\/\/doi.org\/10.1002\/advs.202417128","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]},"assertion":[{"value":"2024-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e17128"}}