{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:01:14Z","timestamp":1792112474248,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["2018KZDXM053"],"award-info":[{"award-number":["2018KZDXM053"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["202102010425"],"award-info":[{"award-number":["202102010425"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700395"],"award-info":[{"award-number":["81700395"]}],"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":["81870217"],"award-info":[{"award-number":["81870217"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["15POST22810024"],"award-info":[{"award-number":["15POST22810024"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Macrophage\u2010rich atherosclerotic arteries are highly active in glycolysis. PFKFB3, a key glycolytic enzyme, has emerged as a potential therapeutic target in atherosclerosis. Small\u2010molecule inhibitors of PFKFB3, such as 3PO and PFK158, have demonstrated efficacy in hampering atherogenesis in preclinical models. However, genetic studies elucidating the role of <jats:italic>Pfkfb3<\/jats:italic> in atherogenesis need to be conducted to validate pharmacological findings and to unveil potential pharmacological side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with global heterozygous or myeloid cell\u2010specific <jats:italic>Pfkfb3<\/jats:italic> deficiency were fed a Western diet (WD), after which atherosclerosis development was determined. Monocyte subsets in atherosclerotic mice and patients were examined by flow cytometry. Monocyte infiltration was assayed by a Ly6C<jats:sup>hi<\/jats:sup> monocyte\u2010specific latex labelling procedure. In situ efferocytosis was assessed on mouse aortic root sections. Additionally, metabolic status, macrophage motility, efferocytosis, and involved mechanisms were analysed in peritoneal macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Global heterozygous or myeloid cell\u2010specific <jats:italic>Pfkfb3<\/jats:italic> deficiency reduced atherogenesis in <jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Mechanistic studies showed that PFKFB3 controlled the proliferation and infiltration of proinflammatory monocytes. Moreover, PFKFB3 expression was associated with inflammatory monocyte expansion in patients with atherosclerotic coronary artery disease. Surprisingly, homozygous loss of <jats:italic>Pfkfb3<\/jats:italic> impaired macrophage efferocytosis and exacerbated atherosclerosis in <jats:italic>Apoe<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Mechanistically, PFKFB3\u2010driven glycolysis was shown to be essential for actin polymerization, thus aiding the efferocytotic function of macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Collectively, these findings suggest the existence of a double\u2010edged sword effect of myeloid PFKFB3 on the pathogenesis of atherosclerosis and highlight the need for caution in developing anti\u2010atherosclerotic strategies that target PFKFB3.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15926","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T16:08:29Z","timestamp":1657814909000},"page":"4974-4991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Gene\u2010dosage effect of <i>Pfkfb3<\/i> on monocyte\/macrophage biology in atherosclerosis"],"prefix":"10.1111","volume":"179","author":[{"given":"Shuai","family":"Guo","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"},{"name":"Department of Radiology the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zou","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixiang","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchuan","family":"Song","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziling","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"},{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Dai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Molecular Target &amp; Clinical Pharmacology, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Center The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Huo","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia Augusta University  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15542"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000550"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.02.193"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.037"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.08.010"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115970"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.306874"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1882"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600474"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.68"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18935"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0735-5"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57559"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313692"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.581641"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901698"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.07.019"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307599"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.316206"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000166517.18801.a7"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150900"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29950"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28549"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.305551"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-95"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.695684"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229395"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318805"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.303041"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00986-7"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201607066"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15926","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15926","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15926","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:50:17Z","timestamp":1692697817000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":36,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1111\/bph.15926"],"URL":"https:\/\/doi.org\/10.1111\/bph.15926","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,3]]},"assertion":[{"value":"2021-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}