The Effects of Exercise on Plaque Volume and Composition in a Mouse Model of Early and Late Life Atherosclerosis

Frontiers in Cardiovascular Medicine

article

Kelly M. Stanton¹  Hongjuan Liu³  Vivian Kienzle¹  Christina Bursill¹  Shisan Bao³  David S. Celermajer¹ 

[1] Clinical Research Group, Heart Research Institute;Faculty of Medicine and Health, The University of Sydney;Discipline of Pathology and School of Medical Science, University of Sydney;Vascular Research Centre, South Australian Health and Medical Research Institute;Faculty of Health and Medical Science, University of Adelaide

关键词: exercise;    atherosclerosis;    cholesterol;    apoE −/− mice;    MMP;    matrix metalloproteinase;    TIMP;    tissue inhibitors of metalloproteinase;   

DOI  :  10.3389/fcvm.2022.837371

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Background Exercise is associated with a less atherogenic lipid profile; however, there is limited research on the effect of exercise on atherosclerotic plaque composition and markers of plaque stability. Methods A total of 110 apolipoprotein ( apo ) E −/− mice were placed on a chow diet and randomly assigned to control or exercise for a period of 10 weeks, commencing either at 12 weeks of age (the early-stage atherosclerosis, EA group) or at 40 weeks of age (the late-stage atherosclerosis, LA group). At the end of the exercise period, blood was assayed for lipids. Histologic analysis of the aortic sinus was undertaken to assess plaque size and composition that includes macrophage content, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and 2). Results A total of 103 mice (38 EA, 65 LA) completed the protocol. In the EA group, exercise reduced plasma total cholesterol (TC) (−16%), free cholesterol (−13%), triglyceride (TG) (−35%), and phospholipid (−27%) levels, when compared to sedentary control mice ( p < 0.01). In the EA group, exercise also significantly reduced plaque stenosis (−25%, p < 0.01), and there were higher levels of elastin (3-fold increase, p < 0.0001) and collagen (11-fold increase, p < 0.0001) in plaques, compared to control mice. There was an increase in plaque MMP-2 content in the exercise group (13% increase, p < 0.05) but no significant difference in macrophage or MCP-1 content. In the LA group, exercise reduced plaque stenosis (−18%, p < 0.05), but there was no significant difference in plaque composition. There was no difference in macrophage, MCP-1, or MMP-2 content in the LA groups. TIMP-1 was lower with exercise in both the EA and LA groups (−59%, p < 0.01 and −51%, p < 0.01 respectively); however, there was no difference in TIMP-2 levels. Conclusion A 10-week exercise period reduces atherosclerotic plaque stenosis when commenced at both early- and late-stage atherosclerosis. Intervening earlier with exercise had a greater beneficial effect on lipids and plaque composition than when starting exercise at a later disease stage.

【 授权许可】

CC BY