Mitochondrial function in vascular endothelial cell in diabetes.
Mitochondrial function in vascular endothelial cell in diabetes.
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DOI：
10.1540/jsmr.48.1
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Makino A
中科院分区：
文献类型：
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作者：
Pangare M;Makino A
糖尿病患者常出现微血管和大血管并发症，内皮功能障碍参与了并发症的发生和发展。血管内皮细胞功能异常导致血管张力增加和动脉粥样硬化，继而导致全身性高血压以及糖尿病患者缺血和中风的发生率增加。线粒体是一种细胞器，既是能量生产的来源，又是细胞存活(如细胞凋亡和细胞发育)和离子稳态(如H+、Ca~(2+))的调节器。内皮线粒体主要负责产生活性氧(ROS)和维持胞浆中的钙离子浓度。越来越多的证据表明线粒体的形态和功能改变与血管内皮细胞功能障碍有关。线粒体分裂增强和/或融合减弱会导致线粒体碎裂，破坏内皮细胞的生理功能。线粒体生物发生异常和线粒体自噬功能障碍会增加受损线粒体的积聚，如不可逆转的去极化或线粒体漏失，从而促进细胞死亡。线粒体ROS生成增加和线粒体内钙超载不仅对内皮功能造成不良适应效应，而且对细胞生存也有潜在的不利影响。在这篇文章中，我们综述了线粒体在内皮功能中的生理和病理生理学作用，尤其是在糖尿病方面。
Micro- and macrovascular complications are commonly seen in diabetic patients and endothelial dysfunction contributes to the development and progression of the complications. Abnormal functions in endothelial cells lead to the increase in vascular tension and atherosclerosis, followed by systemic hypertension as well as increased incident of ischemia and stroke in diabetic patients. Mitochondria are organelles serving as a source of energy production and as regulators of cell survival (e.g., apoptosis and cell development) and ion homeostasis (e.g., H+, Ca2+). Endothelial mitochondria are mainly responsible for generation of reactive oxygen species (ROS) and maintaining the Ca2+ concentration in the cytosol. There is increasing evidence that mitochondrial morphological and functional changes are implicated in vascular endothelial dysfunction. Enhanced mitochondrial fission and/or attenuated fusion lead to mitochondrial fragmentation and disrupt the endothelial physiological function. Abnormal mitochondrial biogenesis and disturbance of mitochondrial autophagy increase the accumulation of damaged mitochondria, such as irreversibly depolarized or leaky mitochondria, and facilitate cell death. Augmented mitochondrial ROS production and Ca2+ overload in mitochondria not only cause the maladaptive effect on the endothelial function, but also are potentially detrimental to cell survival. In this article, we review the physiological and pathophysiological role of mitochondria in endothelial function with special focus on diabetes.