{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:49:44Z","timestamp":1788904184095,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008092","name":"Science and Technology Bureau of Jinhua City","doi-asserted-by":"publisher","award":["2024-3-032"],"award-info":[{"award-number":["2024-3-032"]}],"id":[{"id":"10.13039\/501100008092","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024-3-032"],"award-info":[{"award-number":["2024-3-032"]}],"id":[{"id":"https:\/\/ror.org\/0347g4065","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerosis (AS) is a major driver of acute cardiovascular events, yet the mechanisms by which exercise stabilizes atherosclerotic plaque remain poorly understood. This study investigated the protective effects of a 12-week treadmill exercise training on plaque stability and macrophage autophagy in ApoE\u2212\/\u2212 mice fed an atherogenic diet. Exercise significantly decreased the serum pro-inflammatory cytokine (tumor necrosis factor-\u03b1) and increased the anti-inflammatory (interleukin-10) mediator in AS mice. Histopathology analysis revealed that exercise improved plaque stability through reduced necrotic core size, increased fibrous cap thickness, and increased collagen content. These improvements were accompanied by decreased lipid accumulation, MMP-9 expression, and macrophage infiltration (CD11b) within the plaque. Mechanistically, exercise activated plaque autophagy, evidenced by increased LC3B fluorescence, elevated LC3II\/I ratio, restoration of Beclin-1, and degradation of p62. Notably, exercise-induced autophagy is specific to plaque-resident macrophages, as demonstrated by strong colocalization of LC3B and CD11b fluorescent signals (Pearson\u2019s correlation coefficient = 0.56). Furthermore, exercise restored fibroblast growth factor 21 (FGF21) levels in both circulation and plaque while concurrently suppressing downstream PI3K\/Akt\/mTOR signaling. Collectively, these findings demonstrated that exercise promotes plaque stability by reducing lipid accumulation, macrophage infiltration, MMP-9 expression, and activation of FGF21. This protection is likely mediated by the activation of macrophage autophagy, specific to plaque-resident macrophages, indicating the cardioprotective benefits of aerobic exercise against AS.<\/jats:p>","DOI":"10.3390\/ijms27114996","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise Improves Atherosclerotic Plaque Stability Through Macrophage Autophagy and the FGF21 Signaling Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Qingbo","family":"Li","sequence":"first","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Mao","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianrui","family":"Lu","sequence":"additional","affiliation":[{"name":"Affiliated Jinhua Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Pan","sequence":"additional","affiliation":[{"name":"Affiliated Jinhua Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8507-564X","authenticated-orcid":false,"given":"Sang Ki","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Sport Science, College of Natural Science, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8258-7911","authenticated-orcid":false,"given":"Lifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1610-5061","authenticated-orcid":false,"given":"Jinming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4038-1368","authenticated-orcid":false,"given":"Mallikarjuna","family":"Korivi","sequence":"additional","affiliation":[{"name":"College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1161\/CIRCRESAHA.118.313816","article-title":"Atherosclerosis","volume":"123","author":"Kobiyama","year":"2018","journal-title":"Circ. 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