Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Medical University of Innsbruck, Innsbruck,
Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Gerontology. 2019;65(1):45-56. doi: 10.1159/000492571. Epub 2018 Aug 30.
Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice.
This study aimed at comparing multiple age-dependent factors that may influence atherosclerosis in a transgenic mouse model.
Young (14 weeks) and aged (49-52 weeks) C57BL/6 wild-type (WT) and atherosclerosis-prone ApoE-/- mice were subjected to physical endurance exercise on a treadmill, with or without a high-fat diet. Five weeks later, the frequencies of regulatory T cells (TREGs) in lymph nodes were assessed by flow cytometry, plasmatic cytokines (interleukin [IL]-1β, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and transforming growth factor [TGF]-β1) levels were determined by Luminex assay. Lipids (cholesterol and triglycerides) and anti-heat shock protein 60 (HSP60) autoantibodies were measured by ELISA. Aortic lesion sizes were assessed by en face imaging. Microarray analysis and qPCR of skeletal muscle gene expression were also performed.
Exercise leads to a reduction of aortic lesions in young ApoE-/- and aged WT mice independent of diet. In most groups, this reduction was followed by an increased proportion of TREGs and TGF-β1 levels. Moreover, gene expression analysis showed that exercise seems to affect the AMPK signaling pathway. In particular, PGC-1α1 mRNA was induced in aged WT mice, whereas it was reduced in young ApoE-/- mice. In addition, GSEA analysis showed a marked reduction in the insulin signaling pathway in aged ApoE-/- mice.
Practicing endurance exercise seems to be enough for reducing early aortic lesion formation, independent of diet. However, this was only true in mice with smaller aortic lesions, since mice with large, advanced, complicated atherosclerotic plaques did not show any reduction in lesion size with exercise training.
动脉粥样硬化是全球范围内导致死亡的主要原因。疾病的发展在很大程度上是由年龄和生活方式因素驱动的，如饮食、身体活动和吸烟。在本研究中，我们研究了运动和饮食对年轻和老年小鼠动脉粥样硬化发展的影响。
本研究旨在比较多种可能影响转基因小鼠模型中动脉粥样硬化的年龄依赖性因素。
对 14 周龄（年轻）和 49-52 周龄（老年）C57BL/6 野生型（WT）和易患动脉粥样硬化的 ApoE-/-小鼠进行跑步机耐力运动，同时或不进行高脂肪饮食。5 周后，通过流式细胞术评估淋巴结中调节性 T 细胞（TREG）的频率，通过 Luminex 测定法测定血浆细胞因子（白细胞介素[IL]-1β、IL-6、IL-10、IL-17、干扰素-γ、肿瘤坏死因子-α和转化生长因子[TGF]-β1）水平。通过 ELISA 测定胆固醇和甘油三酯水平和抗热休克蛋白 60（HSP60）自身抗体。通过正面成像评估主动脉病变大小。还进行了骨骼肌基因表达的微阵列分析和 qPCR。
运动可减少年轻 ApoE-/-和老年 WT 小鼠的主动脉病变，无论饮食如何。在大多数组中，这种减少伴随着 TREG 和 TGF-β1 水平的增加。此外，基因表达分析表明，运动似乎影响 AMPK 信号通路。特别是，PGC-1α1 mRNA 在老年 WT 小鼠中被诱导，而在年轻 ApoE-/-小鼠中被降低。此外，GSEA 分析显示，老年 ApoE-/-小鼠胰岛素信号通路明显减少。
进行耐力运动似乎足以减少早期主动脉病变的形成，而与饮食无关。然而，这仅在主动脉病变较小的小鼠中是正确的，因为运动训练不能减少具有大、晚期、复杂动脉粥样硬化斑块的小鼠的病变大小。
