Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.
Physiol Res. 2019 Oct 25;68(5):727-737. doi: 10.33549/physiolres.934110. Epub 2019 Aug 19.
Histone deacetylase (HDAC) inhibitors have shown beneficial effects in animal models of cardiovascular diseases. We hypothesized that HDAC inhibitor, sodium valproate (VPA), has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy induced by transverse aortic constriction (TAC). Sections of the heart were visualized after hematoxylin and eosin staining, picrosirius red staining and immunohistochemistry. The expression of genes related to cardiac hypertrophy, fibrosis, and oxidative stress was determined by quantitative real-time polymerase chain reaction. The aortic ring tension analysis was conducted using both the ascending aorta and descending thoracic aorta. TAC increased the expression of hypertrophic, fibrotic, and oxidative stress genes, which was attenuated by VPA. In the ascending aorta with intact endothelium, there was a significant decrease in the relaxation response, which was recovered by VPA treatment. These results indicate that VPA has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy.
组蛋白去乙酰化酶(HDAC)抑制剂在心血管疾病的动物模型中显示出有益的效果。我们假设,HDAC 抑制剂丙戊酸钠(VPA)在由主动脉缩窄(TAC)引起的压力超负荷性心肌肥厚的大鼠中具有心脏和血管保护作用。通过苏木精和伊红染色、苦味酸天狼猩红染色和免疫组织化学观察心脏切片。通过实时定量聚合酶链反应确定与心肌肥厚、纤维化和氧化应激相关的基因的表达。使用升主动脉和降胸主动脉进行主动脉环张力分析。TAC 增加了肥厚、纤维化和氧化应激基因的表达,而 VPA 则减弱了这种表达。在完整内皮的升主动脉中,舒张反应显著降低,而 VPA 处理可使其恢复。这些结果表明,VPA 对压力超负荷性心肌肥厚大鼠具有心脏和血管保护作用。