Cell Death Research and Therapy Group, Department of Cellular and Molecular Medicine, KU Leuven, Belgium.
VIB Center for Cancer Biology Research, Leuven, Belgium.
FEBS Lett. 2021 Jun;595(11):1497-1511. doi: 10.1002/1873-3468.14087. Epub 2021 Apr 24.
Autophagy, the major lysosomal pathway for the degradation and recycling of cytoplasmic materials, is increasingly recognized as a major player in endothelial cell (EC) biology and vascular pathology. Particularly in solid tumors, tumor microenvironmental stress such as hypoxia, nutrient deprivation, inflammatory mediators, and metabolic aberrations stimulates autophagy in tumor-associated blood vessels. Increased autophagy in ECs may serve as a mechanism to alleviate stress and restrict exacerbated inflammatory responses. However, increased autophagy in tumor-associated ECs can re-model metabolic pathways and affect the trafficking and surface availability of key mediators and regulators of the interplay between EC and immune cells. In line with this, heightened EC autophagy is involved in pathological angiogenesis, inflammatory, and immune responses. Here, we review major cellular and molecular mechanisms regulated by autophagy in ECs under physiological conditions and discuss recent evidence implicating EC autophagy in tumor angiogenesis and immunosurveillance.
自噬是细胞内溶酶体降解和回收细胞质物质的主要途径，它在血管内皮细胞（EC）生物学和血管病理学中越来越被认为是一个主要的参与者。特别是在实体瘤中，肿瘤微环境中的应激，如缺氧、营养剥夺、炎症介质和代谢异常，会刺激肿瘤相关血管中的自噬。EC 中的自噬增加可能是一种减轻应激和限制炎症反应加剧的机制。然而，肿瘤相关 EC 中的自噬增加可以重塑代谢途径，并影响关键介质的运输和表面可用性，以及调节 EC 和免疫细胞之间相互作用的调节剂。与此一致的是，EC 自噬的增加参与了病理性血管生成、炎症和免疫反应。在这里，我们综述了自噬在生理条件下调节 EC 的主要细胞和分子机制，并讨论了最近的证据表明 EC 自噬在肿瘤血管生成和免疫监视中的作用。
