Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Kaul Genetics Building Room 802A, 720 20th Street South, Birmingham, AL 35233, USA.
Cardiovasc Res. 2022 Jun 29;118(8):1885-1903. doi: 10.1093/cvr/cvab198.
The histone deacetylases (HDACs) are a family of enzymes that catalyse lysine deacetylation of both histone and non-histone proteins. Here, we review, summarize, and provide perspectives on the literature regarding one such HDAC, HDAC1, in endothelial biology. In the endothelium, HDAC1 mediates the effects of external and environmental stimuli by regulating major endothelial functions such as angiogenesis, inflammatory signalling, redox homeostasis, and nitric oxide signalling. Angiogenesis is most often, but not exclusively, repressed by endothelial HDAC1. The regulation of inflammatory signalling is more complex as HDAC1 promotes or suppresses inflammatory signalling depending upon the environmental stimuli. HDAC1 is protective in models of atherosclerosis where loss of HDAC1 results in increased cytokine and cell adhesion molecule (CAM) abundance. In other models, HDAC1 promotes inflammation by increasing CAMs and repressing claudin-5 expression. Consistently, from many investigations, HDAC1 decreases antioxidant enzyme expression and nitric oxide production in the endothelium. HDAC1 decreases antioxidant enzyme expression through the deacetylation of histones and transcription factors, and also regulates nitric oxide production through regulating both the expression and activity of nitric oxide synthase 3. The HDAC1-dependent regulation of endothelial function through the deacetylation of both histone and non-histone proteins ultimately impacts whole animal physiology and health.
组蛋白去乙酰化酶（HDACs）是一类能够催化组蛋白和非组蛋白赖氨酸去乙酰化的酶。在这里，我们综述并提供了关于内皮生物学中一种 HDAC，即 HDAC1 的文献观点。在内皮细胞中，HDAC1 通过调节主要内皮功能，如血管生成、炎症信号、氧化还原平衡和一氧化氮信号，介导外部和环境刺激的作用。血管生成通常但并非排他性地被内皮细胞 HDAC1 抑制。炎症信号的调节更为复杂，因为 HDAC1 根据环境刺激促进或抑制炎症信号。在动脉粥样硬化模型中，HDAC1 具有保护作用，因为 HDAC1 的缺失会导致细胞因子和细胞黏附分子（CAM）的丰度增加。在其他模型中，HDAC1 通过增加 CAMs 和抑制 Claudin-5 表达来促进炎症。一致的是，许多研究表明，HDAC1 会降低内皮细胞中的抗氧化酶表达和一氧化氮产生。HDAC1 通过去乙酰化组蛋白和转录因子来降低抗氧化酶的表达，还通过调节一氧化氮合酶 3 的表达和活性来调节一氧化氮的产生。HDAC1 通过对组蛋白和非组蛋白的去乙酰化调节内皮功能，最终影响整个动物的生理和健康。
