Endothelial cell metabolism in normal and diseased vasculature.
Endothelial cell metabolism in normal and diseased vasculature.
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DOI：
10.1161/circresaha.116.302855
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发表时间：
2015-03-27
影响因子：
20.1
通讯作者：
Carmeliet P
中科院分区：
文献类型：
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作者：
Eelen G;de Zeeuw P;Simons M;Carmeliet P
高等生物体依赖于一个封闭的心血管循环系统，血管为远处的组织提供重要的营养和氧气。毫不奇怪，血管病变是最危及生命的疾病之一。大多数这些血管病变的关键是（功能障碍）内皮细胞（EC），血管腔的细胞内衬。内皮细胞在血管出芽过程中表现出从静止状态迅速转变为高度迁移和增殖状态的显著能力。长期以来，这种血管生成转换一直被认为是由血管生成生长因子（例如血管内皮生长因子; VEGF）和其他信号（例如Notch）单独决定的，但最近的研究结果表明，它也是由EC中的代谢转换驱动的。此外，代谢的这些变化甚至可以覆盖诱导血管发芽的信号。在这里，我们回顾EC代谢如何在正常和功能障碍/患病的脉管系统之间有所不同，以及它如何与其他细胞类型的代谢相关或影响其他细胞类型的代谢。我们专注于肿瘤血管中的内皮细胞和动脉粥样硬化中的糖尿病内皮细胞的生物学，作为内皮代谢在关键病理过程中的作用的例子。最后，目前以及未开发的“EC代谢”为中心的治疗途径进行了讨论。
Higher organisms rely on a closed cardiovascular circulatory system with blood vessels supplying vital nutrients and oxygen to distant tissues. Not surprisingly, vascular pathologies rank among the most life-threatening diseases. At the crux of most of these vascular pathologies are (dysfunctional) endothelial cells (ECs), the cells lining the blood vessel lumen. ECs display the remarkable capability to switch rapidly from a quiescent state to a highly migratory and proliferative state during vessel sprouting. This angiogenic switch has long been considered to be dictated by angiogenic growth factors (eg vascular endothelial growth factor; VEGF) and other signals (eg Notch) alone, but recent findings show that it is also driven by a metabolic switch in ECs. Furthermore, these changes in metabolism may even override signals inducing vessel sprouting. Here, we review how EC metabolism differs between the normal and dysfunctional/diseased vasculature and how it relates to or impacts the metabolism of other cell types contributing to the pathology. We focus on the biology of ECs in tumor blood vessel and diabetic ECs in atherosclerosis as examples of the role of endothelial metabolism in key pathological processes. Finally, current as well as unexplored ‘EC metabolism’-centric therapeutic avenues are discussed.