{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:49:08Z","timestamp":1791985748490,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    MD\u20101 plays significant roles in various pathological processes closely associated with cardiovascular diseases through its functions in different cell types. However, the critical effects and molecular mechanisms mediated by MD\u20101 in macrophages involved in the development of atherosclerosis remain elusive. In this study, we observed that the expression of MD\u20101 was upregulated in atherosclerotic plaques derived from human carotid arteries, as analysed through the Gene Expression Omnibus database. Additionally, MD\u20101 expression was elevated in the aortas of hyperlipidemic ApoE\u2010deficient mice and in oxidised low\u2010density lipoprotein\u2010stimulated bone marrow\u2010derived macrophages, as demonstrated by RT\u2010PCR and western blot analyses. Furthermore, MD\u20101 expression exhibited strong co\u2010localisation with macrophages, as confirmed by double immunofluorescence staining. Notably, MD\u20101\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice subjected to a high\u2010fat diet displayed a significant reduction in atherosclerotic plaques throughout the entire aorta, aortic root, and brachiocephalic arteries. Moreover, the plaques in MD\u20101\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were more stable, characterised by a decreased necrotic core size, reduced macrophage infiltration, and lower lipid deposition, alongside an increased accumulation of collagen and smooth muscle cells. Bone marrow transplantation from MD\u20101\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice to ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice markedly attenuated the development of atherosclerosis. This attenuation was associated with an enhanced anti\u2010inflammatory macrophage phenotype and a reduction in pro\u2010inflammatory macrophage polarisation. Similar effects of MD\u20101 ablation on macrophage behaviour were also observed in\u00a0vitro. Mechanistically, MD\u20101 deficiency inhibited the cyclic GMP\u2010AMP synthase\u2010stimulator of interferon genes\u2010TANK\u2010binding kinase 1\u2010IRF3 pathway, thereby attenuating NLRP3 inflammasome activation in macrophages. However, the use of the STING agonist DMXAA counteracted the effects of MD\u20101 deficiency on macrophage polarisation. Our findings reveal MD\u20101 promotes pro\u2010inflammatory (M1\u2010like) macrophage polarisation in atherosclerosis by inhibiting NLRP3 inflammasome activation via a cGAS\u2010STING dependent pathway. These results suggest that MD\u20101 neutralisation could be a potential therapeutic strategy for atherosclerosis management.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70288","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:14:06Z","timestamp":1791983646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MD<\/scp>\n                    \u20101 Deficiency Mitigates Atherosclerosis by Inhibiting\n                    <scp>NLRP3<\/scp>\n                    Inflammasome Activation via\n                    <scp>cGAS<\/scp>\n                    \u2010\n                    <scp>STING<\/scp>\n                    Dependent Pathway in Macrophages"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-0319","authenticated-orcid":false,"given":"Fang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hubei Provincial 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hubei Provincial Clinical Research Center for Cardiovascular Interventional Diagnosis and Treatment Zhongnan Hospital, Wuhan University  Wuhan China"},{"name":"Institute of Myocardial Injury and Repair Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hubei Provincial Clinical Research Center for Cardiovascular Interventional Diagnosis and Treatment Zhongnan Hospital, Wuhan University  Wuhan 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