Scheede-Bergdahl Celena, Bergdahl Andreas
a Department of Kinesiology & Physical Education, McGill University, Montreal, QC H2W 1S4, Canada.
b McGill Research Centre for Physical Activity & Health, McGill University, Montreal, QC H2W 1S4, Canada.
Can J Physiol Pharmacol. 2017 Dec;95(12):1473-1479. doi: 10.1139/cjpp-2017-0227. Epub 2017 Aug 28.
Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation.
动脉粥样硬化是西方世界发病和死亡的主要原因之一。尽管这种疾病的临床表现已有充分记录，但其病因和进展仍有待充分了解。最近，线粒体已被认为与动脉粥样硬化发展过程中的重要细胞过程有关。尽管线粒体与动脉粥样硬化之间存在联系，但该疾病的早期机制尚未阐明。本项目的目的是探讨线粒体在血管平滑肌（VSMC）去分化中的作用。使用了一种小鼠体外模型，即在无血清培养基中对主动脉组织进行器官培养。通过高分辨率呼吸测定法测量线粒体功能。通过免疫印迹评估与VSMC表型转换相关的蛋白质以及线粒体密度。研究结果表明，在VSMC去分化过程中，线粒体内在复合物I的活性显著上调。还发现磷酸化与氧化之间的偶联减少，表明ADP:ATP比值更高。该数据表明电子传递链中的泄漏增加，并且线粒体功能特别是在复合物I处发生改变。本项目提供了有关线粒体在早期动脉粥样硬化过程中的作用的重要信息，并且线粒体功能和表达的可检测变化与VSMC去分化有关。
