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Mitochondrial abnormalities are related to the dysfunction of circulating endothelial-colony-forming cells in moyamoya disease : 모야모야병에서 혈관내피전구세포와 미토콘드리아의 이상에 관한 연구

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Authors

최정원

Advisor
김승기
Major
의과대학 의학과
Issue Date
2018-02
Publisher
서울대학교 대학원
Keywords
Cerebrovascular diseaseEndothelial colony–forming cellEndothelial progenitor cellMitochondriaMoyamoyaReactive oxygen species
Description
학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 2. 김승기.
Abstract
Introduction: Moyamoya disease (MMD) is a unique cerebrovascular disorder characterized by the progressive occlusion of the bilateral internal carotid artery. Although diverse genetic analyses of MMD have been performed, the etiology of MMD has not been fully clarified. Endothelial colony–forming cells (ECFCs), which were previously termed endothelial progenitor cells, play an important role in the pathogenesis of MMD. In this study, we performed morphological and functional studies of the mitochondria of ECFCs from MMD patients to present new insights into the pathogenesis of MMD.

Methods: The morphology of the ECFCs from the MMD patients and normal healthy volunteers was examined under both a transmission electron microscope and a confocal laser scanning microscope following staining with MitoTracker Red. The oxygen consumption rates (OCRs), mitochondrial membrane potentials (MMPs), intracellular Ca2+ concentrations, mitochondrial enzyme activities, and reactive oxygen species (ROS) levels were measured. The functional activity of the ECFCs was evaluated using a capillary tube formation assay.

Results: The ECFCs from the MMD patients displayed a disrupted mitochondrial morphology, including a shorter and more circular shape. The mitochondria of the ECFCs from the MMD patients exhibited functional abnormalities, which were assessed as a decreased OCR and increased intracellular Ca2+ concentration. Moreover, the ECFCs from MMD patients showed increased ROS levels. Interestingly, treatment with a ROS scavenger not only rescued the mitochondrial abnormalities, but also restored the angiogenic activity of the ECFCs from the MMD patients.

Conclusions: The mitochondria of the ECFCs from the MMD patients exhibit morphological and functional abnormalities compared to normal ECFCs. This finding suggests that the mitochondrial abnormalities may have a possible role in the pathogenesis of MMD.
Language
English
URI
https://hdl.handle.net/10371/141029
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