title: Mesenchymal stem cells preconditioned with trimetazidine promote neovascularization of hearts under hypoxia/reoxygenation injury.
abstract: BACKGROUND
  Cell-based angiogenesis is a promising treatment for ischemic diseases; however, survival of implanted cells is impaired by the ischemic microenvironment. In this study, mesenchymal stem cells (MSCs) for cell transplantation were preconditioned with trimetazidine (TMZ). We hypothesized that TMZ enhances the survival rate of MSCs under hypoxic stimuli through up-regulation of HIF1-α.
  
  
  RESULTS
  Bone marrow-derived rat mesenchymal stem cells were preconditioned with 10 μM TMZ for 6 h. TMZ preconditioning of MSCs remarkably increased cell viability and the expression of HIF1-α and Bcl-2, when cells were under hypoxia/reoxygenation (H/R) stimuli. But the protective effects of TMZ were abolished after knocking down of HIF-1α. Three days after implantation of the cells into the peri-ischemic zone of rat myocardial ischemia-reperfusion (I/R) injury model, survival of the TMZ-preconditioned MSCs was high. Furthermore, capillary density and cardiac function were significantly better in the rats implanted with TMZ-preconditioned MSCs 28 days after cell injection.
  
  
  CONCLUSIONS
  TMZ preconditioning increased the survival rate of MSCs, through up-regulation of HIF1-α, thus contributing to neovascularization and improved cardiac function of rats subjected to myocardial I/R injury.
authors.affiliation: Department of Cardiology of The First Affiliated Hospital, Soochow University Suzhou 215006, China ; Present address: Department of Cardiology of Xinyu People's Hospital Xinyu, Jiangxi Province, 338000, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology of The First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Group of Translational Stem Cell Research, Osaka Medical College Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Cardiology of The First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hui
keywords: Angiogenesis; hypoxia/reoxygenation injury; ischemia; neovascularization; stem cells; trimetazidine