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综述:内皮细胞在缺氧状态下的行为

Review: behaviour of endothelial cells faced with hypoxia.

作者信息

Paternotte E, Gaucher C, Labrude P, Stoltz J-F, Menu P

机构信息

Ingénierie Cellulaire et Tissulaire, LEMTA-UMR 7563, IFR 111, Faculté de Médecine, Nancy-Université, Vandoeuvre-lès-Nancy, France.

出版信息

Biomed Mater Eng. 2008;18(4-5):295-9.

Abstract

Hypoxia is a diminution of oxygen quantity delivered to tissue for cellular need to product energy. Hypoxia derives from two major conditions in health diseases: anemia and ischemia. Anemic hypoxia comes from damage to O(2) transport like red blood cells diminution or disease. Ischemic hypoxia is a diminution of blood flow following a diminution of blood volume after a hemorrhagic shock. After hypoxia, vessels dilate to increase blood flow allowing a better oxygenation of peripheral tissues. This vasodilation appears immediately after the beginning of hypoxia and can be maintained during several hours. Today, the molecular mechanisms of this vasodilation stay unclear. But it seems that potassic channels, ATP concentration and medium acidification in addition to vasodilator/vasoconstrictor balance play a great role to facilitate the oxygenation of the ischemic areas.As endothelial cells (EC) are lining the vasculature, they are always in contact with blood, which carries, amongst other compounds, oxygen. In this way, they are the first target for an oxygen partial pressure (PO(2)) diminution. EC, through different mechanosensors, can sense a variation in PO(2) and adapt their metabolism to maintain ATP production. Under hypoxia, EC switch into hypoxic metabolism, leading to the production of reactive oxygen species (ROS). Indeed, when PO(2) is low, the respiratory chain in the mitochondria runs slower. Furthermore, cytochrome C capacity to trap O(2) is reduced; this phenomenon alters the cellular redox potential and leads to the accumulation of electrons that induce the formation of ROS.This review presents an overview of the behaviour of endothelial cells face to hypoxia. We propose to focus on nitric oxide, hypoxia inducible factor (HIF), lactate and ROS productions. Then we present the different mode of culture of EC under hypoxia. Finally, we conclude on the difficulty to study hypoxia because of the various types of system developed to reproduce this phenomenon and the different signalling ways that can be activated.

摘要

缺氧是指输送到组织的氧气量减少,无法满足细胞产生能量的需求。缺氧主要源于健康疾病中的两种主要情况:贫血和局部缺血。贫血性缺氧源于氧气运输受损,如红细胞减少或疾病。缺血性缺氧是指失血性休克后血容量减少导致血流减少。缺氧后,血管扩张以增加血流量,使外周组织得到更好的氧合。这种血管舒张在缺氧开始后立即出现,并可持续数小时。目前,这种血管舒张的分子机制尚不清楚。但似乎钾通道、ATP浓度和介质酸化以及血管舒张剂/血管收缩剂平衡在促进缺血区域的氧合方面起着重要作用。由于内皮细胞(EC)排列在血管系统内,它们始终与携带氧气等多种化合物的血液接触。因此,它们是氧分压(PO₂)降低的首要靶点。内皮细胞通过不同的机械传感器,可以感知PO₂的变化,并调整其代谢以维持ATP的产生。在缺氧状态下,内皮细胞转变为缺氧代谢,导致活性氧(ROS)的产生。事实上,当PO₂较低时,线粒体中的呼吸链运行较慢。此外,细胞色素C捕获O₂的能力降低;这种现象改变了细胞的氧化还原电位,导致电子积累,进而诱导ROS的形成。本综述概述了内皮细胞在缺氧情况下的行为。我们建议关注一氧化氮、缺氧诱导因子(HIF)、乳酸和ROS的产生。然后我们介绍了内皮细胞在缺氧条件下的不同培养模式。最后,我们得出结论:由于为重现这一现象而开发的各种系统以及可能被激活的不同信号传导方式,研究缺氧存在困难。

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