{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:05:26Z","timestamp":1791313526560,"version":"4.3.1"},"reference-count":31,"publisher":"Georg Thieme Verlag KG","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background Clinical observation suggests the atheroprotective effect of\n                    chloroquine and its derivatives, while its mechanism remains unclear. This study\n                    aimed to observe the protective effect of chloroquine against atherosclerosis\n                    and explore the underlying mechanism.<\/jats:p><jats:p>\n          Methods Ataxia telangiectasia mutated (ATM) wild-type or haploinsufficient\n                    apolipoprotein-E-knockout\n                        (ATM+\/+ApoE\u2212\/\u2212\n                    or\n                        ATM+\/\u2212ApoE\u2212\/\u2212)\n                    mice were treated with different dosages of chloroquine. Anti-CD25 antibody was\n                    used to deplete natural Tregs in\n                        ATM+\/+ApoE\u2212\/\u2212\n                    mice. The atherosclerotic burden in different groups of mice was comprehensively\n                    evaluated by H&amp;E staining and Masson staining. The effect of chloroquine\n                    on the regulatory T cells (Tregs) was assessed in vivo and in vitro by flow\n                    cytometry and immunohistochemical staining. The expression of related proteins\n                    was detected by real-time polymerase chain reaction and western blotting.<\/jats:p><jats:p>\n          Results In\n                        ATM+\/+ApoE\u2212\/\u2212\n                    mice, chloroquine alleviated atherosclerotic lesions, stabilized the plaque, and\n                    increased Treg counts in the atherosclerotic lesions and spleens. However, in\n                    ATM haploinsufficient mice\n                        (ATM+\/\u2212ApoE\u2212\/\u2212),\n                    chloroquine no longer prevented atherosclerosis or impacted Treg counts.\n                    Abolishing Treg cells using an anti-CD25 antibody in vivo abrogated the\n                    atheroprotective effect of chloroquine. In vitro, chloroquine promoted the\n                    differentiation of Tregs from na\u00efve T cells, which was accompanied by\n                    enhanced ATM\/AMP-activated protein kinase (AMPK) activity and reduced\n                    downstream mammalian target of rapamycin (mTOR) activity.<\/jats:p><jats:p>\n          Discussion These findings suggest that chloroquine ameliorates\n                    atherosclerosis and stabilizes plaque by modulating Tregs differentiation\n                    through the regulation of the ATM\/AMPK\/mTOR pathway.<\/jats:p>","DOI":"10.1055\/a-2201-8728","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T23:43:54Z","timestamp":1701906234000},"page":"676-685","source":"Crossref","is-referenced-by-count":6,"title":["Chloroquine Alleviates Atherosclerosis by Modulating Regulatory T\n                    Cells Through the ATM\/AMPK\/mTOR Signaling Pathway in\n                            ApoE\n            \u2212\/\u2212\n           Mice"],"prefix":"10.1055","volume":"131","author":[{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, West China Hospital,\n                    Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Research and Application, Institute of Blood\n                    Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical\n                    College (CAMS & PUMC), Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sichuan Provincial People\u2019s\n                    Hospital, University of Electronic Science and Technology of China, Chengdu,\n                    China"},{"name":"Chinese Academy of Sciences, Sichuan Translational Medicine Research\n                    Hospital, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaorong","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy,\n                    West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentong","family":"Meng","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy,\n                    West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, West China Hospital, Sichuan\n                    University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Mo","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy,\n                    West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, West China Hospital,\n                    Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, West China Hospital,\n                    Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"903126","DOI":"10.3389\/fcvm.2022.903126","article-title":"Global burden attributable to high low-density lipoprotein-cholesterol from 1990\n                    to 2019","volume":"9","author":"H Du","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e069066","DOI":"10.1136\/bmj-2021-069066","article-title":"PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: A\n                    clinical practice guideline with risk-stratified recommendations","volume":"377","author":"Q Hao","year":"2022","journal-title":"BMJ"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1161\/01.RES.0000029784.15893.10","article-title":"Innate and adaptive immunity in the pathogenesis of 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Delgoffe","year":"2009","journal-title":"Immunity"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4049\/jimmunol.1701477","article-title":"mTOR complex 1 signaling regulates the generation and function of central and\n                    effector Foxp3(+) regulatory T cells","volume":"201","author":"I H Sun","year":"2018","journal-title":"J Immunol"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2201-8728.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T23:44:47Z","timestamp":1701906287000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2201-8728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,6]]},"published-print":{"date-parts":[[2023,12]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2201-8728","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12]]}}}