Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
Biomed Res Int. 2020 Jul 24;2020:4705615. doi: 10.1155/2020/4705615. eCollection 2020.
The use of histone deacetylase (HDAC) inhibitor is a novel therapeutic strategy for cardiovascular disease. Studies have shown that many HDAC inhibitors have the ability to reduce the aortic remodeling in various animal models. We hypothesized that the HDAC inhibitor, MGCD0103 (MGCD), attenuates aortic remodeling in rats under pressure overload-induced by transverse aortic constriction (TAC). The aortic ring tension analysis was conducted using the thoracic aorta. Sections of the aorta were visualized after hematoxylin and eosin, trichrome, and Verhoeff-van Gieson staining, and immunohistochemistry. The expression of genes related to aortic remodeling (, , and ) and angiotensin receptors ( and ) was determined by quantitative real-time polymerase chain reaction. There was a significant decrease in relaxation of the aorta when treated with MGCD. Fibrosis of the aortic wall and expression of angiotensin receptors increased in TAC rats, which was attenuated by MGCD. These results indicate that MGCD, an HDAC inhibitor, attenuates aortic remodeling in rats with TAC-induced pressure overload rats and may serve as a potential therapeutic target of antiaortic remodeling in pressure overload-induced hypertension-related diseases.
组蛋白去乙酰化酶（HDAC）抑制剂的使用是心血管疾病的一种新的治疗策略。研究表明，许多 HDAC 抑制剂具有减少各种动物模型主动脉重塑的能力。我们假设 HDAC 抑制剂 MGCD0103（MGCD）可减轻由横主动脉缩窄（TAC）引起的压力超负荷大鼠的主动脉重塑。采用胸主动脉进行主动脉环张力分析。用苏木精和伊红、三色和 Verhoeff-van Gieson 染色以及免疫组织化学对主动脉切片进行可视化。通过实时定量聚合酶链反应确定与主动脉重塑相关的基因（、和）和血管紧张素受体（和）的表达。用 MGCD 处理后，主动脉的舒张明显减少。TAC 大鼠的主动脉壁纤维化和血管紧张素受体表达增加，MGCD 可减轻这种增加。这些结果表明，HDAC 抑制剂 MGCD 可减轻 TAC 诱导的压力超负荷大鼠的主动脉重塑，可能成为与压力超负荷相关高血压疾病中抗主动脉重塑的潜在治疗靶点。
