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The Role of High-Density Lipoproteins in Endothelial Cell Metabolism and Diabetes-Impaired Angiogenesis

机译:高密度脂蛋白在内皮细胞代谢和糖尿病致血管生成中的作用

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摘要

Diabetes mellitus affects millions of people worldwide and is associated with devastating vascular complications. A number of these complications, such as impaired wound healing and poor coronary collateral circulation, are characterised by impaired ischaemia-driven angiogenesis. There is increasing evidence that high-density lipoproteins (HDL) can rescue diabetes-impaired angiogenesis through a number of mechanisms, including the modulation of endothelial cell metabolic reprogramming. Endothelial cell metabolic reprogramming in response to tissue ischaemia is a driver of angiogenesis and is dysregulated by diabetes. Specifically, diabetes impairs pathways that allow endothelial cells to upregulate glycolysis in response to hypoxia adequately and impairs suppression of mitochondrial respiration. HDL rescues the impairment of the central hypoxia signalling pathway, which regulates these metabolic changes, and this may underpin several of its known pro-angiogenic effects. This review discusses the current understanding of endothelial cell metabolism and how diabetes leads to its dysregulation whilst examining the various positive effects of HDL on endothelial cell function.
机译:糖尿病影响全球数百万人,并与破坏性的血管并发症相关。这些并发症中的许多并发症(例如伤口愈合不良和冠状动脉侧支循环不良)的特征在于缺血驱动的血管生成受损。越来越多的证据表明,高密度脂蛋白(HDL)可通过多种机制来挽救糖尿病受损的血管生成,包括调节内皮细胞代谢重编程。响应于组织局部缺血的内皮细胞代谢重编程是血管生成的驱动力,并且被糖尿病失调。具体地说,糖尿病会损害通路,使内皮细胞充分响应缺氧而上调糖酵解,并削弱线粒体呼吸的抑制作用。 HDL挽救了调节这些代谢变化的中枢低氧信号通路的损伤,这可能是其一些已知的促血管生成作用的基础。这篇综述讨论了目前对内皮细胞代谢的理解以及糖尿病如何导致其失调,同时研究了HDL对内皮细胞功能的各种积极作用。

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