Gilead Colorado Inc, 3333 Walnut St, Boulder, CO 80301, USA.
Circ Res. 2010 Feb 5;106(2):272-84. doi: 10.1161/CIRCRESAHA.109.209338.
Acetylation of histone and nonhistone proteins provides a key mechanism for controlling signaling and gene expression in heart and kidney. Pharmacological inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors has shown promise in preclinical models of cardiovascular and renal disease. Efficacy of HDAC inhibitors appears to be governed by pleiotropic salutary actions on a variety of cell types and pathophysiological processes, including myocyte hypertrophy, fibrosis, inflammation and epithelial-to-mesenchymal transition, and occurs at compound concentrations below the threshold required to elicit toxic side effects. We review the roles of acetylation/deacetylation in the heart and kidney and provide rationale for extending HDAC inhibitors into clinical testing for indications involving these organs.
组蛋白和非组蛋白的乙酰化提供了一种控制心脏和肾脏中信号转导和基因表达的关键机制。用组蛋白去乙酰化酶 (HDAC) 抑制剂抑制蛋白质去乙酰化的药理作用已在心血管和肾脏疾病的临床前模型中显示出前景。HDAC 抑制剂的疗效似乎受多种细胞类型和病理生理过程的有益作用的影响，包括心肌肥大、纤维化、炎症和上皮-间充质转化，并且在低于引起毒性副作用所需的阈值的化合物浓度下发生。我们综述了乙酰化/去乙酰化在心脏和肾脏中的作用，并为将 HDAC 抑制剂扩展到涉及这些器官的适应证的临床测试提供了依据。
