Mechanisms underlying protective effects of trimetazidine on endothelial progenitor cells biological functions against H₂O₂-induced injury: Involvement of antioxidation and Akt/eNOS signaling pathways

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• 作者：Qinqin Wu ; Benling Qi ; ^{benlingdoctor@yahoo.cn} ; Yun Liu ; Bei Cheng ; Lihua Liu ; Yuanyuan Li ; Qian Wang
• 关键词：Trimetazidine ; Endothelial progenitor cells ; Oxidative stress ; Akt/eNOS signaling pathway ; Ischemic heart disease
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：5 May, 2013
• 年：2013
• 卷：707
• 期：1-3
• 页码：87-94
• 全文大小：1007 K

文摘

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 ¦ÌM) and the preliminary mechanisms involved in vitro. The results showed that pretreatment of EPCs with TMZ (10 ¦ÌM) 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.