title: Trimetazidine protects against hypoxia-reperfusion-induced cardiomyocyte apoptosis by increasing microRNA-21 expression.
abstract: Myocardial tissue injury caused by ischemia and hypoxia is a major cause of fatal diseases, including coronary atherosclerosis resulting from myocardial infarction and stroke. Trimetazidine (TMZ), as an anti-ischemic and antioxidant agent, has been demonstrated to preventing ischemia/reperfusion-induced cardiomyocyte apoptosis. However, the anti-apoptosis mechanism of TMZ has not been fully elucidated. The present study demonstrated that miR-21 involved trimetazidine-induced anti-apoptosis during H/R injury in H9C2 cell. In this study, TMZ increased miR-21 expression which further upregulated the Akt signaling activity via suppressing the expression of phosphatase and tensin homolog (PTEN) in H/R H9C2 cell. The increased activity of Akt signaling decreased the ratio of Bax/Bcl-2 and the expression of caspase-3 and inhibited H/R induced apoptosis. In conclusion, this study revealed the mechanism that TMZ up-regulated miR-21 expression, then miR-21 targeted PTEN increasing the PI3K pathway and finally the activation of this pathway counteracted the apoptotic effect of hypoxia/reperfusion.
authors.affiliation: Department of Cardiology, The Third Xiangya Hospital of Central South University 138 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The Third Xiangya Hospital of Central South University 138 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The Third Xiangya Hospital of Central South University 138 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, China.
authors.forename: An-Ying
authors.initials: AY
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014292:Trimetazidine / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3; D014292:Trimetazidine
keywords: H/R injury; PTEN/Akt pathway; Trimetazidine; miR-21