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内皮细胞稳态和血管疾病交界处的自噬作用。

Autophagy at the interface of endothelial cell homeostasis and vascular disease.

机构信息

University/BHF Centre for Cardiovascular Science, QMRI, University of Edinburgh, UK.

UCL Institute of Ophthalmology, London, UK.

出版信息

FEBS J. 2022 Jun;289(11):2976-2991. doi: 10.1111/febs.15873. Epub 2021 May 2.

DOI:10.1111/febs.15873
PMID:33934518
Abstract

Autophagy is an essential intracellular process for cellular quality control. It enables cell homeostasis through the selective degradation of harmful protein aggregates and damaged organelles. Autophagy is essential for recycling nutrients, generating energy to maintain cell viability in most tissues and during adverse conditions such as hypoxia/ischaemia. The progressive understanding of the mechanisms modulating autophagy in the vasculature has recently led numerous studies to link intact autophagic responses with endothelial cell (EC) homeostasis and function. Preserved autophagic flux within the ECs has an essential role in maintaining their physiological characteristics, whereas defective autophagy can promote endothelial pro-inflammatory and atherogenic phenotype. However, we still lack a good knowledge of the complete molecular repertoire controlling various aspects of endothelial autophagy and how this is associated with vascular diseases. Here, we provide an overview of the current state of the art of autophagy in ECs. We review the discoveries that have so far defined autophagy as an essential mechanism in vascular biology and analyse how autophagy influences ECs behaviour in vascular disease. Finally, we emphasise opportunities for compounds to regulate autophagy in ECs and discuss the challenges of exploiting them to resolve vascular disease.

摘要

自噬是细胞内质量控制的一个基本过程。它通过选择性降解有害的蛋白质聚集体和受损的细胞器来维持细胞内稳态。自噬对于回收营养物质、产生能量以维持大多数组织中的细胞活力以及在缺氧/缺血等不利条件下至关重要。对调节血管中自噬机制的机制的深入了解最近导致许多研究将完整的自噬反应与内皮细胞 (EC) 的内稳态和功能联系起来。在 EC 中保持完整的自噬流对于维持其生理特征至关重要,而自噬缺陷可促进内皮细胞的促炎和动脉粥样硬化表型。然而,我们仍然缺乏对控制内皮细胞自噬各个方面的完整分子谱的充分了解,以及这种自噬与血管疾病的关联。在这里,我们概述了 EC 中自噬的最新研究进展。我们回顾了迄今为止将自噬定义为血管生物学中基本机制的发现,并分析了自噬如何影响血管疾病中的 EC 行为。最后,我们强调了调节 EC 中自噬的化合物的机会,并讨论了利用它们来解决血管疾病的挑战。

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