{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:55:00Z","timestamp":1790848500133,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic reprogramming contributes to vascular dysfunction in diabetic atherosclerosis, but the mechanisms linking hyperglycemia\u2010induced metabolic alterations to extracellular matrix remodeling in vascular smooth muscle cells remain incompletely understood. This study investigated whether liraglutide modulates vascular smooth muscle cell metabolism and plaque remodeling under diabetic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Primary vascular smooth muscle cells were exposed to normal glucose, high glucose, or high glucose plus liraglutide. Cellular bioenergetics, mitochondrial function, oxidative stress, extracellular matrix remodeling, and AMPK\/PGC\u20101\u03b1, mTOR, and HIF\u20101\u03b1 signaling were assessed. In\n                      <jats:italic>vivo<\/jats:italic>\n                      , diabetic ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were treated with liraglutide for 12 weeks, followed by evaluation of metabolic parameters, aortic root plaque burden, lipid deposition, collagen content, and plaque\u2010associated signaling markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High glucose impaired mitochondrial respiration, enhanced glycolysis, reduced mitochondrial membrane potential, increased mitochondrial reactive oxygen species, and promoted mitochondrial fragmentation and extracellular matrix remodeling in vascular smooth muscle cells. Liraglutide restored mitochondrial function, activated AMPK\/PGC\u20101\u03b1 signaling, suppressed mTOR activation and HIF\u20101\u03b1 accumulation, reduced collagen I, MMP\u20102, and MMP\u20109 expression, and partially restored elastin levels. In diabetic ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, liraglutide improved systemic metabolic parameters, reduced atherosclerotic plaque burden and lipid accumulation, increased plaque collagen content, restored plaque p\u2010AMPK expression, and reduced HIF\u20101\u03b1 and MMP\u20109 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Liraglutide attenuates hyperglycemia\u2010induced metabolic reprogramming and extracellular matrix remodeling in vascular smooth muscle cells and improves plaque stability in diabetic atherosclerosis. These effects are associated with restoration of AMPK\/PGC\u20101\u03b1 signaling, inhibition of mTOR activation, suppression of HIF\u20101\u03b1 accumulation, and improved mitochondrial homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70398","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:16:26Z","timestamp":1785838586000},"page":"1695-1707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liraglutide reprograms vascular smooth muscle cell metabolism to suppress extracellular matrix remodeling in diabetic atherosclerosis"],"prefix":"10.1111","volume":"17","author":[{"given":"Kun","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Operating Room Shaanxi Provincial People's Hospital  Xi'an 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Yan'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Shaanxi Provincial People's Hospital  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-5450","authenticated-orcid":false,"given":"Zhongwei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Yan'an University  Yan'an China"},{"name":"Department of Cardiology Shaanxi Provincial People's Hospital  Xi'an China"},{"name":"Shaanxi Cardiovascular and Cerebrovascular Disease Precision Medicine \u201cBelt and Road\u201d Joint Laboratory  Xi'an China"},{"name":"School of Life Sciences and Technology, Northwestern Polytechnical University  Xi'an 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