{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:34:48Z","timestamp":1791466488211,"version":"4.3.4"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Diabetes is known to accelerate atherosclerosis and increase plaque instability. However, there has been a lack of suitable animal models to study the effect of diabetes on plaque instability. We hypothesized that the tandem stenosis mouse model, which reflects plaque instability\/rupture as seen in patients, can be applied to study the effects of diabetes and respective therapeutics on plaque instability\/rupture.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice at 7\u00a0weeks of age were rendered diabetic with streptozotocin and 5\u00a0weeks later were surgically subjected to tandem stenosis in the right carotid artery and fed with a high\u2010fat diet for 7\u00a0weeks. As a promising new antidiabetic drug class, a sodium glucose co\u2010transporter 2 inhibitor was tested in this new model. Diabetic mice showed an increase in the size of unstable atherosclerotic plaques and in the plaque instability markers MCP\u20101, CD68, and necrotic core size. Mice treated with dapagliflozin demonstrated attenuated glucose and triglyceride levels. Importantly, these mice demonstrated plaque stabilization with enhanced collagen accumulation, increased fibrosis, increased cap\u2010to\u2010lesion height ratios, and significant upregulation of the vasculoprotective NADPH oxidase 4 expression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The tandem stenosis mouse model in combination with the application of streptozotocin represents a highly suitable and unique mouse model for studying plaque destabilization under diabetic conditions. Furthermore, for the first time, we provide evidence of plaque\u2010stabilizing effects of sodium\u2010glucose co\u2010transporter 2 inhibitor. Our data also suggest that this newly developed mouse model is an attractive preclinical tool for testing antidiabetic drugs for the highly sought\u2010after potential to stabilize atherosclerotic plaques.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022761","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T11:35:05Z","timestamp":1640950505000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Sodium\u2010Glucose Co\u2010Transporter 2 (SGLT2) Inhibitor Dapagliflozin Stabilizes Diabetes\u2010Induced Atherosclerotic Plaque Instability"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5387-5818","authenticated-orcid":false,"given":"Yung\u2010Chih","family":"Chen","sequence":"first","affiliation":[{"name":"Baker Heart &amp; Diabetes Institute Melbourne Australia"},{"name":"Central Clinical School Monash University Melbourne Australia"},{"name":"Department of Cardiometabolic Health University of Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2192-5822","authenticated-orcid":false,"given":"Karin","family":"Jandeleit\u2010Dahm","sequence":"additional","affiliation":[{"name":"Department of Diabetes Monash University Melbourne Australia"},{"name":"German Diabetes Centre Leibniz Centre for Diabetes Research at Heinrich Heine University Dusseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-2258","authenticated-orcid":false,"given":"Karlheinz","family":"Peter","sequence":"additional","affiliation":[{"name":"Baker Heart &amp; Diabetes Institute Melbourne Australia"},{"name":"Central Clinical School Monash University Melbourne Australia"},{"name":"Department of Cardiometabolic Health University of Melbourne Australia"},{"name":"Department of Cardiology The Alfred Hospital Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.039996"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301562"},{"key":"e_1_3_2_4_2","article-title":"The tandem stenosis mouse model: towards understanding, imaging, and preventing atherosclerotic plaque instability and rupture","author":"Noonan J","year":"2020","unstructured":"Noonan J, Bobik A, Peter K. The tandem stenosis mouse model: towards understanding, imaging, and preventing atherosclerotic plaque instability and rupture. Br J Pharmacol. 2020. doi: 10.1111\/bph.15356","journal-title":"Br J Pharmacol"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00138-x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy419"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18935"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa094"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.307012"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30344-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab128"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.02.028"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4158-2"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.7.1813"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.022761","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:10:44Z","timestamp":1715598644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.022761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,4]]}},"alternative-id":["10.1161\/JAHA.121.022761"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.022761","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]},"assertion":[{"value":"2021-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e022761"}}