Aging compounds western diet-associated large artery endothelial dysfunction in mice: prevention by voluntary aerobic exercise.

Aging compounds western diet-associated large artery endothelial dysfunction in mice: prevention by voluntary aerobic exercise.
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DOI:
10.1016/j.exger.2013.08.001
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发表时间:
2013-11
影响因子:
3.9
通讯作者:
Seal, Douglas R.
Seal, Douglas R.
中科院分区:
医学2区
文献类型:
--
作者:
Lesniewski, Lisa A.;Zigler, Melanie L.;Durrant, Jessica R.;Nowlan, Molly J.;Folian, Brian J.;Donato, Anthony J.;Seal, Douglas R.

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我们检验了这样一个假设,即老化会加剧暴露于常见生理应激源的负面血管后果,即,通过诱导与超氧化物相关的一氧化氮(NO)生物利用度的降低来消耗“西方”(高脂肪/高蔗糖)饮食(WD),并且这将通过自愿有氧运动来预防。测定了青年人颈动脉的刚度增量和内皮依赖性舒张功能(EDD),(5.4±0.3个月,N=20)和老年(30.4±0.2 mo,N=19)饲喂正常饲料的雄性B6 D2 F1小鼠(NC:17%脂肪,0%蔗糖)或西方饮食(40%脂肪,19%蔗糖)饮食,并在标准笼或配备有转轮的笼中饲养10-14周。与年轻NC小鼠相比,老年NC小鼠(P<0.05)以及年轻(P<0.01)和老年(P<0.01)WD喂养小鼠的刚度增量更高,但WD没有进一步增加老年小鼠的刚度。在笼内对照小鼠中,NC喂养的老年小鼠和WD喂养的年轻小鼠的EDD均降低17%(P<0.05)。老年小鼠摄入WD后EDD进一步降低20%(P<0.05)。与年老的WD喂养的对照小鼠相比,年老的WD喂养的小鼠中能够使用转轮的增加刚度低28%,EDD高38%(P<0.05),并且与年轻的NC喂养的对照没有差异。轮跑也倾向于改善EDD(+9%,P=0.11),但在年轻的WD喂养小鼠中不会增加僵硬。离体治疗与超氧化物清除剂TEMPOL和NO抑制剂L-NAME废除这些各自的影响,年龄,WD和自愿运行EDD。WD的摄入诱导老年和年轻的成年B6 D2 F1小鼠内皮功能障碍的程度相似,这些影响是由NO生物利用度的超氧化物依赖性损伤介导的。然而,老年和WD的组合,在我们的老龄化社会中常见,导致内皮功能的显著的、附加的降低。重要的是,定期自愿有氧运动降低动脉僵硬度,并防止WD对内皮功能的不良影响,在老年动物通过防止超氧化物抑制NO。这些研究结果可能有重要意义的动脉老化和预防年龄相关的心血管疾病。
We tested the hypothesis that aging will exacerbate the negative vascular consequences of exposure to a common physiological stressor, i.e., consumption of a “western” (high fat/high sucrose) diet (WD) by inducing superoxide-associated reductions in nitric oxide (NO) bioavailability, and that this would be prevented by voluntary aerobic exercise. Incremental stiffness and endothelium-dependent dilation (EDD) were measured in the carotid arteries of young (5.4±0.3 mo, N=20) and old (30.4±0.2 mo, N=19) male B6D2F1 mice fed normal chow (NC: 17% fat, 0% sucrose) or a western diet (40% fat, 19% sucrose) diet and housed in either standard cages or cages equipped with running wheels for 10–14 weeks. Incremental stiffness was higher in old NC (P<0.05) and both young (P<0.01) and old (P<0.01) WD fed mice compared with young NC mice, but WD did not further increase stiffness in the old mice. In cage control mice, EDD was 17% lower in both NC fed old mice and young WD fed mice (P<0.05). Consumption of WD by old mice led to a further 20% reduction in EDD (P<0.05). Incremental stiffness was 28% lower and EDD was 38% greater in old WD fed mice with access to running wheels vs. old WD fed control mice (P<0.05) and not different from young NC fed controls. Wheel running also tended to improve EDD (+9%, P=0.11), but not incremental stiffness in young WD fed mice. Ex vivo treatment with the superoxide scavenger TEMPOL and NO inhibitor L-NAME abolished these respective effects of age, WD and voluntary running on EDD. Ingestion of a WD induces similar degrees of endothelial dysfunction in old and young adult B6D2F1 mice, and these effects are mediated by a superoxide-dependent impairment of NO bioavailability. However, the combination of old age and WD, a common occurrence in our aging society, results in a marked, additive reduction in endothelial function. Importantly, regular voluntary aerobic exercise reduces arterial stiffness and protects against the adverse influence of WD on endothelial function in old animals by preventing superoxide suppression of NO. These findings may have important implications for arterial aging and the prevention of age-associated cardiovascular diseases.
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