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首页> 外文学位 >Effects of laminar shear stress on mitochondrial DNA integrity in endothelial cells.
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Effects of laminar shear stress on mitochondrial DNA integrity in endothelial cells.

机译：层流切应力对内皮细胞线粒体DNA完整性的影响。

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摘要

Purpose/hypothesis: Regular practice of exercise is the most effective non-pharmacological intervention that improves vascular health, which is thought to be mediated by a repeated exposure of vessel walls to increased hemodynamic shear stress (SS). Mitochondria have been shown to be essential cellular structures responsible for a wide variety of vascular functions, and its impairment is often associated with cardiovascular disease. However, researches on vascular mitochondrial adaptations to SS are in a very early stage and many questions remain unresolved. The objective of this study is to investigate the effect of exercise preconditioning on endothelial mitochondria in an angiotensin (Ang) II-induced hypertension model. It was hypothesized that exercise preconditioning prevents Ang II induced-hypertensive phenotypes by improving mitochondrial homeostasis in the endothelium.;Methods: High-magnitude laminar SS (LSS) (20 dyne/cm2) was applied to human aortic endothelial cells (HAECs) using a cone-and-plate shear apparatus for 48 hours. Either LSS-preconditioned or static flow-situated HAECs were incubated with Ang II. In in vivo experiments, C57BL/6J mice were singly housed with or without a voluntary running wheel for 7 weeks. Ang II or saline was infused in a constant rate using an implantable osmotic pump for the last 2 weeks of the experimental period. Mitochondrial membrane potential (Deltapsim) and mitoROS production were measured using fluorochrome molecular probe-based microscopic techniques, and mtDNA damage was assessed by a long amplicon quantitative PCR (LA-QPCR) method.;Results: In HAECs, LSS preconditioning attenuated Ang II-induced mitochondrial dysfunction, which was evidenced by decreased mitoROS generation, increased Deltapsim, and reduced mtDNA damage. Likewise, in aortic tissues, Ang II-induced mitochondrial phenotypic changes (i.e. mitoROS production, mtDNA damage and Deltapsim reduction) were significantly reduced in exercise-preconditioned mice compared to sedentary controls. Moreover, Ang II-induced blood pressure elevation was completely blocked in exercise preconditioned animals.;Conclusion: Taken together, high-magnitude LSS improves endothelial function by enhancing mtDNA integrity and mitochondrial function. These findings further support the idea that aerobic exercise is a prominent life-style modification strategy to prevent hypertension by targeting dysfunctional mitochondria in the vessel wall.
机译：目的/假设：定期运动是改善血管健康的最有效的非药物干预措施，据信这是通过使血管壁反复暴露于增加的血流动力学切应力（SS）来介导的。线粒体已被证明是负责多种血管功能的重要细胞结构，其损伤通常与心血管疾病有关。然而，有关血管线粒体对SS适应性的研究仍处于早期阶段，许多问题仍未解决。这项研究的目的是调查运动预处理对血管紧张素（Ang）II诱导的高血压模型中内皮线粒体的影响。假设运动预处理可通过改善内皮中的线粒体稳态来防止Ang II诱导的高血压表型。锥板剪切仪持续48小时。将经过LSS预处理或静态流动的HAEC与Ang II一起孵育。在体内实验中，将C57BL / 6J小鼠单独饲养有或没有自愿行走轮7周。在实验期的最后2周内，使用植入式渗透泵以恒定速率注入Ang II或盐水。使用基于荧光染料分子探针的显微镜技术测量线粒体膜电位（Deltapsim）和mitoROS产生，并通过长扩增子定量PCR（LA-QPCR）方法评估mtDNA损伤。诱导的线粒体功能障碍，这可通过减少mitoROS生成，增加Deltapsim和减少mtDNA损伤来证明。同样，在运动后预处理的小鼠中，与久坐的对照组相比，在主动脉组织中，Ang II诱导的线粒体表型变化（即mitoROS产生，mtDNA损伤和Deltapsim降低）显着降低。此外，Ang II诱导的血压升高在运动预处理动物中被完全阻止。结论：综上所述，高强度LSS通过增强mtDNA完整性和线粒体功能来改善内皮功能。这些发现进一步支持了有氧运动是通过针对血管壁线粒体功能障碍来预防高血压的一种重要生活方式改变策略。

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  • 作者

    Kim, Boa.;

  • 作者单位

    Temple University.;

  • 授予单位 Temple University.;
  • 学科 Health Sciences Recreation.;Biology Physiology.;Biology General.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 175 p.
  • 总页数 175
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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