Mitochondrial dysfunction in vascular endothelial cells in diabetes mellitus
Liu, Sara Weiran
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Diabetes mellitus type II has quickly become one of the biggest health concerns worldwide. One of the greatest consequences of diabetes lies in the fact that it is a potent risk factor for cardiovascular disease. Diabetes mellitus leads to endothelial dysfunction, which contributes to the pathogenesis of cardiovascular disease. The endothelium is the "control center" for vascular homeostasis, regulating important processes such as vasodilation and constriction, thrombosis and thrombolysis, inflammation, and smooth muscle proliferation. As such, endothelial dysfunction leads to macrovascular and microvascular pathologies. A recently recognized mechanism of endothelial dysfunction is altered mitochondrial function, which leads to increased harmful reactive oxygen species generation. Recent studies in our laboratory indicate that diabetes alters the balance between mitochondrial fission and fusion to promote mitochondrial fragmentation and a loss of normal mitochondrial networks. In the present study, we investigated a potential mechanism of mitochondrial fragmentation in endothelial cells exposed to high glucose concentration. Our prior studies have shown that 30 mM glucose leads to a marked increase in mitochondrial ROS production. We exposed human aortic endothelial cells to normal (5 mM) and high (30 mM) glucose and measured mitochondrial membrane potential using tetramethylrhodamine ethyl ester and assessed mitochondrial network extent using a mitochondrial protein tagged green fluorescent protein (CellLight Mitochondria-GFP). High glucose was associated with an increase in mitochondrial membrane potential and mitochondrial fragmentation. Silencing expression of Complex Ill of the electron transport chain for 48 hours using siRNA prevented mitochondrial fragmentation . These findings implicate mitochondrial Complex III as a source of glucose-induced ROS production that contributes to mitochondrial fragmentation. Ongoing studies will determine whether Complex III contributes to altered membrane potential and impaired endothelial production of nitric oxide under diabetic conditions. These findings further implicate altered mitochondrial function in diabetes-associated endothelial dysfunction.
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