Regular Exercise Training Prevents Aortic Valve Disease in Low-Density Lipoprotein-Receptor-Deficient Mice
Regular Exercise Training Prevents Aortic Valve Disease in Low-Density Lipoprotein-Receptor-Deficient Mice
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DOI：
10.1161/circulationaha.109.892224
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发表时间：
2010-02-16
期刊：
影响因子：
37.8
通讯作者：
Linke, Axel
中科院分区：
文献类型：
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作者：
Matsumoto, Yasuharu;Adams, Volker;Linke, Axel
方法与结果：4周龄低密度脂蛋白受体缺陷小鼠(n=94)随机分为4组：1组(对照组)，正常饮食+久坐活动；2组(胆固醇组)，胆固醇饮食+久坐活动；3组(常规ET组)，胆固醇饮食+常规ET(60min/d，5天/周)，共16周；4组(间歇性运动组)，胆固醇饮食+间歇性ET(1天/周)，共16周。20周龄时取材进行组织学分析。与对照组相比，胆固醇组的主动脉瓣厚度明显增加。重要的是，与胆固醇组相比，规律但非偶然的ET显著降低了主动脉瓣厚度(对照组31.3+/-3.0微米，胆固醇50.1+/-3.4微米，规律运动30.4+/-1.2微米，偶尔运动48.9+/-3.2微米)。免疫组织化学显示胆固醇饮食中断，常规ET维持了主动脉瓣表面内皮细胞的完整性。此外，胆固醇组大鼠血清髓过氧化物酶、巨噬细胞和氧化型低密度脂蛋白积聚、原位超氧化物歧化、肌成纤维细胞/成骨细胞表型活化和矿化增加，而常规ET组则减少。聚合酶链式反应显示胆固醇组α-平滑肌肌动蛋白、骨形态发生蛋白-2、矮小相关转录因子-2和碱性磷酸酶的信使RNA表达增加，而常规ET组这些信使RNA表达减少。结论：在低密度脂蛋白受体缺陷小鼠中，常规ET通过多种机制预防主动脉瓣硬化，包括保护内皮完整性，减少炎症和氧化应激，抑制成骨途径。(发行量。2010年；121：759-767。)
Background-Regular exercise training (ET) slows the progression of atherosclerotic lesions, reduces oxidative stress, and increases nitric oxide bioavailability, all of which may be expected to improve degenerative aortic valve disease.Methods and Results-Four-week-old low-density lipoprotein-receptor-deficient mice (n=94) were randomly divided into 4 groups: Group 1 (control group), normal diet plus sedentary activity; group 2 (cholesterol group), cholesterol diet plus sedentary activity; group 3 (regular ET group), cholesterol diet plus regular ET (60 min/day, 5 days/week) for 16 weeks; and group 4 (occasional exercise group), cholesterol diet plus occasional ET (1 day/week) for 16 weeks. At 20 weeks of age, histological analysis was performed. A significant increase in aortic valve thickness was evident in the cholesterol group compared with the control group. Importantly, regular but not occasional ET significantly reduced aortic valve thickness compared with the cholesterol group (control 31.3+/-3.0 mu m, cholesterol 50.1+/-3.4 mu m, regular exercise 30.4+/-1.2 mu m, and occasional exercise 48.9+/-3.2 mu m). Immunohistochemistry revealed that a cholesterol diet disrupted and regular ET preserved endothelial integrity on the aortic valve surface. Furthermore, serum myeloperoxidase, accumulation of macrophages and oxidized low-density lipoprotein, in situ superoxide, activated myofibroblasts/osteoblast phenotypes, and mineralization were increased in the cholesterol group but were decreased by regular ET. Polymerase chain reaction revealed increased messenger RNA expression for alpha-smooth muscle actin, bone morphogenetic protein-2, runt-related transcription factor-2, and alkaline phosphatase in the cholesterol group, whereas these were diminished by regular ET. Moreover, regular ET significantly increased circulating levels of fetuin-A compared with the cholesterol group.Conclusions-In the low-density lipoprotein-receptor-deficient mouse, regular ET prevents aortic valve sclerosis by numerous mechanisms, including preservation of endothelial integrity, reduction in inflammation and oxidative stress, and inhibition of the osteogenic pathway. (Circulation. 2010; 121: 759-767.)