title: Mechanisms underlying protective effects of trimetazidine on endothelial progenitor cells biological functions against H2O2-induced injury: involvement of antioxidation and Akt/eNOS signaling pathways.
abstract: 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.
authors.affiliation: Department of Geriatrics, Union Hospital, Tongji Medicine College, Huazhong University Science & Technology, 1277 Jie-Fang Avenue, Wuhan 430022, People's Republic of China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Wu
authors.forename: Benling
authors.initials: B
authors.lastname: Qi
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Bei
authors.initials: B
authors.lastname: Cheng
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008315:Malondialdehyde / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014292:Trimetazidine / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D012263:Ribonucleosides; C023764:triciribine; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D014292:Trimetazidine