Department of Geriatrics, Union Hospital, Tongji Medicine College, Huazhong University Science & Technology, 1277 Jie-Fang Avenue, Wuhan 430022, People's Republic of China.
Eur J Pharmacol. 2013 May 5;707(1-3):87-94. doi: 10.1016/j.ejphar.2013.03.027. Epub 2013 Mar 23.
Trimetazidine (TMZ) is a widely used drug exerting cardioprotective effects against ischemic heart disease through a number of mechanisms in conditions of oxidative stress. However, there are few data regarding the effects of TMZ on endothelial lineage, especially endothelial progenitor cells (EPCs). Thus, we sought to investigate whether TMZ could protect EPCs against oxidative stress injury induced by H2O2 (100 µM) and the preliminary mechanisms involved in vitro. The results showed that pretreatment of EPCs with TMZ (10 µM) protected the proliferation, adhesion, migration, and apoptosis of EPCs against H2O2, accompanied by an increase in superoxide dismutase (SOD) activity, a decrease in malonaldehyde (MDA) content, and increases in eNOS, Akt phosphorylation, and NO production. These TMZ-mediated beneficial effects on EPCs could be attenuated by pre-incubation with the Akt inhibitor triciribine. In conclusion, the present study demonstrates that TMZ ameliorated H2O2-induced impairment of biological functions in EPCs with the involvement of antioxidation and Akt/eNOS signaling pathway. These findings suggest that TMZ mediating preservation of EPCs may contribute to its cardioprotective effects on ischemic heart disease.
曲美他嗪（TMZ）是一种广泛使用的药物，通过多种机制在氧化应激条件下发挥抗缺血性心脏病的作用。然而，关于 TMZ 对内皮谱系，特别是内皮祖细胞（EPCs）的影响的数据很少。因此，我们试图研究 TMZ 是否可以保护 EPCs 免受 H2O2（100µM）诱导的氧化应激损伤，以及体外涉及的初步机制。结果表明，用 TMZ（10µM）预处理 EPCs 可以保护 EPCs 的增殖、黏附、迁移和凋亡免受 H2O2 的影响，同时增加超氧化物歧化酶（SOD）活性，降低丙二醛（MDA）含量，并增加 eNOS、Akt 磷酸化和 NO 生成。Akt 抑制剂曲美他嗪预处理可减弱 TMZ 对 EPCs 的这些有益作用。总之，本研究表明，TMZ 通过抗氧化和 Akt/eNOS 信号通路改善了 H2O2 诱导的 EPCs 生物功能障碍。这些发现表明，TMZ 介导的 EPCs 保存可能有助于其对缺血性心脏病的心脏保护作用。
