Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, Colorado 80045-0508, USA.
Mol Med. 2011 May-Jun;17(5-6):434-41. doi: 10.2119/molmed.2011.00022. Epub 2011 Jan 20.
Cardiovascular insults such as myocardial infarction and chronic hypertension can trigger the heart to undergo a remodeling process characterized by myocyte hypertrophy, myocyte death and fibrosis, often resulting in impaired cardiac function and heart failure. Pathological cardiac remodeling is associated with inflammation, and therapeutic approaches targeting inflammatory cascades have shown promise in patients with heart failure. Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models, suggesting unforeseen potential for this class of compounds for the treatment of heart failure. In addition to their beneficial effects on myocardial cells, HDAC inhibitors have potent antiinflammatory actions. This review highlights the roles of HDACs in the heart and the potential for using HDAC inhibitors as broad-based immunomodulators for the treatment of human heart failure.
心血管损伤，如心肌梗死和慢性高血压，可引发心肌细胞肥大、心肌细胞死亡和纤维化等重构过程，导致心功能障碍和心力衰竭。病理性心脏重构与炎症有关，靶向炎症级联反应的治疗方法在心衰患者中显示出良好的效果。小分子组蛋白去乙酰化酶（HDAC）抑制剂可阻止动物模型中的不良心脏重构，这表明该类化合物在心力衰竭治疗方面具有意外的潜力。除了对心肌细胞的有益作用外，HDAC 抑制剂还具有强大的抗炎作用。本综述强调了 HDAC 在心脏中的作用，以及将 HDAC 抑制剂用作治疗人类心力衰竭的广泛免疫调节剂的潜力。
