Nature Reviews Cardiology ( IF 41.7 ) Pub Date : 2022-07-19 , DOI: 10.1038/s41569-022-00739-0 Samuel I Bloom 1 , Md Torikul Islam 1 , Lisa A Lesniewski 1, 2, 3 , Anthony J Donato 1, 2, 3, 4
Endothelial cells are located at the crucial interface between circulating blood and semi-solid tissues and have many important roles in maintaining systemic physiological function. The vascular endothelium is particularly susceptible to pathogenic stimuli that activate tumour suppressor pathways leading to cellular senescence. We now understand that senescent endothelial cells are highly active, secretory and pro-inflammatory, and have an aberrant morphological phenotype. Moreover, endothelial senescence has been identified as an important contributor to various cardiovascular and metabolic diseases. In this Review, we discuss the consequences of endothelial cell exposure to damaging stimuli (haemodynamic forces and circulating and endothelial-derived factors) and the cellular and molecular mechanisms that induce endothelial cell senescence. We also discuss how endothelial cell senescence causes arterial dysfunction and contributes to clinical cardiovascular diseases and metabolic disorders. Finally, we summarize the latest evidence on the effect of eliminating senescent endothelial cells (senolysis) and identify important remaining questions to be addressed in future studies.
中文翻译:
内皮细胞衰老的机制和后果
内皮细胞位于循环血液和半实体组织之间的关键界面,在维持全身生理功能方面起着许多重要作用。血管内皮特别容易受到致病性刺激的影响,这些刺激会激活导致细胞衰老的肿瘤抑制途径。我们现在了解到衰老的内皮细胞具有高度活跃、分泌和促炎作用,并且具有异常的形态表型。此外,内皮衰老已被确定为各种心血管和代谢疾病的重要因素。在这篇综述中,我们讨论了内皮细胞暴露于有害刺激(血流动力学力和循环和内皮衍生因子)的后果以及诱导内皮细胞衰老的细胞和分子机制。我们还讨论了内皮细胞衰老如何导致动脉功能障碍并导致临床心血管疾病和代谢紊乱。最后,我们总结了关于消除衰老内皮细胞 (senolysis) 效果的最新证据,并确定了未来研究中需要解决的重要遗留问题。