Junshu Wang, Yihang Cai, Mohammad Ismail Hajary Sagor, Yunqi Chu, Fang Liu, Tingjun Wang
{"title":"Irisin protects against atherosclerosis in ApoE<sup>-/-</sup> mice by suppressing the migration of vascular smooth muscle cell via PI3K-Akt-cofilin.","authors":"Junshu Wang, Yihang Cai, Mohammad Ismail Hajary Sagor, Yunqi Chu, Fang Liu, Tingjun Wang","doi":"10.1007/s11010-025-05414-9","DOIUrl":null,"url":null,"abstract":"<p><p>Irisin, a myokine secreted by the skeletal muscles during exercise, exerts atheroprotective effects. However, the precise molecular mechanisms that underlie these effects remain incompletely elucidated. This study aimed to investigate the effect of irisin on atherosclerosis and vascular smooth muscle cell (VSMC) migration, and to explore the role of cofilin-mediated cytoskeletal remodeling in the atheroprotective effect of irisin. In vivo, irisin was administered to high-fat diet-fed ApoE<sup>-/-</sup> mice. Dyslipidemia in these mice was alleviated by irisin treatment. Atherosclerotic lesion assessment via Oil Red O staining, Masson's trichrome staining, and alpha-smooth muscle actin (a-SMA) immunofluorescence staining revealed that irisin significantly attenuated atherosclerotic plaque burden, necrotic core size, and VSMC area within the aortic tissue of ApoE<sup>-/-</sup> mice. However, the atheroprotective effect of irisin was partially reversed when ApoE<sup>-/-</sup> mice were cotreated with an integrin αVβ5 inhibitor. In vitro, irisin supplementation decreased platelet-derived growth factor (PDGF)-induced VSMC migration, determined by wound healing assay and transwell migration assay. Furthermore, irisin treatment reversed the elevated expression of p-PI3K and p-Akt as well as the decreased expression of p-cofilin observed both in the aorta of ApoE<sup>-/-</sup> mice and in PDGF-stimulated VSMCs. The effects of irisin on p-PI3K, p-Akt, and p-cofilin expression were partially blocked by cotreatment with an integrin αVβ5 inhibitor or PI3K activator. The decreased expression of p-cofilin in PDGF-stimulated VSMCs was partially blocked by PI3K inhibitor. Systemic irisin administration confers protection against atherosclerosis in ApoE<sup>-/-</sup> mice. Mechanistically, this beneficial effect involves suppression of the PI3K-Akt signaling pathway, which modulates cofilin-mediated cytoskeletal remodeling to regulate VSMC migration.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05414-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Irisin, a myokine secreted by the skeletal muscles during exercise, exerts atheroprotective effects. However, the precise molecular mechanisms that underlie these effects remain incompletely elucidated. This study aimed to investigate the effect of irisin on atherosclerosis and vascular smooth muscle cell (VSMC) migration, and to explore the role of cofilin-mediated cytoskeletal remodeling in the atheroprotective effect of irisin. In vivo, irisin was administered to high-fat diet-fed ApoE-/- mice. Dyslipidemia in these mice was alleviated by irisin treatment. Atherosclerotic lesion assessment via Oil Red O staining, Masson's trichrome staining, and alpha-smooth muscle actin (a-SMA) immunofluorescence staining revealed that irisin significantly attenuated atherosclerotic plaque burden, necrotic core size, and VSMC area within the aortic tissue of ApoE-/- mice. However, the atheroprotective effect of irisin was partially reversed when ApoE-/- mice were cotreated with an integrin αVβ5 inhibitor. In vitro, irisin supplementation decreased platelet-derived growth factor (PDGF)-induced VSMC migration, determined by wound healing assay and transwell migration assay. Furthermore, irisin treatment reversed the elevated expression of p-PI3K and p-Akt as well as the decreased expression of p-cofilin observed both in the aorta of ApoE-/- mice and in PDGF-stimulated VSMCs. The effects of irisin on p-PI3K, p-Akt, and p-cofilin expression were partially blocked by cotreatment with an integrin αVβ5 inhibitor or PI3K activator. The decreased expression of p-cofilin in PDGF-stimulated VSMCs was partially blocked by PI3K inhibitor. Systemic irisin administration confers protection against atherosclerosis in ApoE-/- mice. Mechanistically, this beneficial effect involves suppression of the PI3K-Akt signaling pathway, which modulates cofilin-mediated cytoskeletal remodeling to regulate VSMC migration.
期刊介绍：
Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell.
In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
