Intrinsic Exercise Capacity and Mitochondrial DNA Lead to Opposing Vascular-Associated Risks.
Intrinsic Exercise Capacity and Mitochondrial DNA Lead to Opposing Vascular-Associated Risks.
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DOI：
10.1093/function/zqaa029
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Wenceslau CF
中科院分区：
文献类型：
--
作者：
Roy S;Edwards JM;Tomcho JC;Schreckenberger Z;Bearss NR;Zhang Y;Morgan EE;Cheng X;Spegele AC;Vijay-Kumar M;McCarthy CG;Koch LG;Joe B;Wenceslau CF
运动能力是人类全因发病率和死亡率的一个强有力的预测因素。然而，将这一有价值的指标与其随后的疾病风险联系起来的相关血流动力学特征是不确定的。此外，运动能力具有相当大的遗传成分，全基因组筛选表明大量的核和线粒体DNA（mtDNA）标记与体能性状显著相关。在大鼠中进行的长期选择实验证实了低容量和高容量跑步者（分别为LCR和HCR）之间的心血管风险差异，为我们提供了一个临床前动物模型来揭示新的机制。在这里，我们评估了LCR和HCR大鼠模型系统在动脉阻力水平上的血管功能差异。与健康和疾病之间的已知划分一致，我们观察到LCR大鼠与HCR大鼠相比存在阻力动脉和血管周围脂肪组织功能障碍，HCR大鼠模拟对健康重要的品质，包括改善血管松弛。独特的是，我们通过产生共质体菌株，其中LCR男性与女性HCR的mtDNA（LCR-mtHCR/Tol）呈现出改善的血管功能。相反，HCR-mtLCR/Tol大鼠显示心功能不全指数。这项研究的结果表明，核基因组和具有高内在运动能力的母系遗传线粒体基因组之间的相互作用是改善血管生理学的重要因素，基于核和mtDNA之间相互作用开发的动物模型是探测后代血管危险因素的有价值的新工具。
Exercise capacity is a strong predictor of all-cause morbidity and mortality in humans. However, the associated hemodynamic traits that link this valuable indicator to its subsequent disease risks are numerable. Additionally, exercise capacity has a substantial heritable component and genome-wide screening indicates a vast amount of nuclear and mitochondrial DNA (mtDNA) markers are significantly associated with traits of physical performance. A long-term selection experiment in rats confirms a divide for cardiovascular risks between low- and high-capacity runners (LCR and HCR, respectively), equipping us with a preclinical animal model to uncover new mechanisms. Here, we evaluated the LCR and HCR rat model system for differences in vascular function at the arterial resistance level. Consistent with the known divide between health and disease, we observed that LCR rats present with resistance artery and perivascular adipose tissue dysfunction compared to HCR rats that mimic qualities important for health, including improved vascular relaxation. Uniquely, we show by generating conplastic strains, which LCR males with mtDNA of female HCR (LCR-mtHCR/Tol) present with improved vascular function. Conversely, HCR-mtLCR/Tol rats displayed indices for cardiac dysfunction. The outcome of this study suggests that the interplay between the nuclear genome and the maternally inherited mitochondrial genome with high intrinsic exercise capacity is a significant factor for improved vascular physiology, and animal models developed on an interaction between nuclear and mtDNA are valuable new tools for probing vascular risk factors in the offspring.
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影响因子：
7.7
作者：
Dhar, Riddhiman;Missarova, Alsu M.;Carey, Lucas B.
通讯作者：
Carey, Lucas B.
DOI：
10.1097/00005768-199802000-00013
发表时间：
1998-02-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Bouchard, C;Daw, EW;Wilmore, JH
通讯作者：
Wilmore, JH
影响因子：
11.1
作者：
Dunham-Snary KJ;Sandel MW;Sammy MJ;Westbrook DG;Xiao R;McMonigle RJ;Ratcliffe WF;Penn A;Young ME;Ballinger SW
通讯作者：
Ballinger SW
DOI：
10.1042/cs20140101
发表时间：
2014-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Chacko BK;Kramer PA;Ravi S;Benavides GA;Mitchell T;Dranka BP;Ferrick D;Singal AK;Ballinger SW;Bailey SM;Hardy RW;Zhang J;Zhi D;Darley-Usmar VM
通讯作者：
Darley-Usmar VM
影响因子：
4.6
作者：
Houstek, Josef;Vrbacky, Marek;Pravenec, Michal
通讯作者：
Pravenec, Michal