Fang Zhi, Wang Xiang, Sun Xiaoran, Hu Wenquan, Miao Qing R
Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, NY, United States.
Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
Front Cell Dev Biol. 2021 Apr 29;9:672447. doi: 10.3389/fcell.2021.672447. eCollection 2021.
Endothelial cell (EC), consisting of the innermost cellular layer of all types of vessels, is not only a barrier composer but also performing multiple functions in physiological processes. It actively controls the vascular tone and the extravasation of water, solutes, and macromolecules; modulates circulating immune cells as well as platelet and leukocyte recruitment/adhesion and activation. In addition, EC also tightly keeps coagulation/fibrinolysis balance and plays a major role in angiogenesis. Therefore, endothelial dysfunction contributes to the pathogenesis of many diseases. Growing pieces of evidence suggest that histone protein acetylation, an epigenetic mark, is altered in ECs under different conditions, and the acetylation status change at different lysine sites on histone protein plays a key role in endothelial dysfunction and involved in hyperglycemia, hypertension, inflammatory disease, cancer and so on. In this review, we highlight the importance of histone acetylation in regulating endothelial functions and discuss the roles of histone acetylation across the transcriptional unit of protein-coding genes in ECs under different disease-related pathophysiological processes. Since histone acetylation changes are conserved and reversible, the knowledge of histone acetylation in endothelial function regulation could provide insights to develop epigenetic interventions in preventing or treating endothelial dysfunction-related diseases.
内皮细胞（EC）构成了所有类型血管的最内层细胞层，它不仅是一种屏障组成部分，还在生理过程中发挥多种功能。它积极控制血管张力以及水、溶质和大分子的外渗；调节循环免疫细胞以及血小板和白细胞的募集/黏附与激活。此外，内皮细胞还紧密维持凝血/纤维蛋白溶解平衡，并在血管生成中起主要作用。因此，内皮功能障碍是许多疾病发病机制的一个因素。越来越多的证据表明，组蛋白乙酰化作为一种表观遗传标记，在不同条件下的内皮细胞中会发生改变，并且组蛋白上不同赖氨酸位点的乙酰化状态变化在内皮功能障碍中起关键作用，涉及高血糖、高血压、炎症性疾病、癌症等。在本综述中，我们强调组蛋白乙酰化在调节内皮功能中的重要性，并讨论在不同疾病相关病理生理过程下，组蛋白乙酰化在编码内皮细胞蛋白质的基因转录单元中的作用。由于组蛋白乙酰化变化具有保守性且可逆，关于组蛋白乙酰化在内皮功能调节方面的知识可为开发预防或治疗内皮功能障碍相关疾病的表观遗传干预措施提供思路。
