title: Hypoxic preconditioning increases survival of cardiac progenitor cells via the pim-1 kinase-mediated anti-apoptotic effect.
abstract: BACKGROUND
  Stem cells transplanted to the ischemic myocardium usually encounter massive cell death within a few days after transplantation, and hypoxic preconditioning (HPC) is currently used as a strategy to prepare stem cells for increased survival and engraftment in the heart. The purpose of this study is to determine whether Pim-1 kinase mediates any beneficial effects of HPC for human cardiac progenitor cells (CPCs).
  
  
  RESULTS
  Human CPCs were isolated from an adult heart auricle and were purified by magnetic-activated cell sorting using c-kit magnetic beads; they were hypoxic preconditioned for 6h. Both Pim-1 and p-Akt were determined. CPCs were assigned to one of the following groups: (1) control (without HPC); (2) HPC; or (3) HPC+I (Pim-1 inhibitor). HPC can promote the survival of CPCs. HPC enhances the expression of Pim-1 kinase in a time-dependent manner, which causes a reduction of proapoptotic elements (cytochrome c and cleaved caspase-3) and the preservation/modulation of important components of the mitochondria (Bcl-2, Bcl-XL and p-Bad), and attenuates mitochondrial damages. All of these protective effects were blocked by a Pim-1 inhibitor.
  
  
  CONCLUSIONS
  Pim-1 plays a pivotal role in the protective effect of HPC for CPCs, and the promotion of the expression of Pim-1 in CPCs can as serve part of molecular therapeutic interventional strategies in the treatment of cardiomyopathy damage by blunting CPC death.
authors.affiliation: Department of Cardiology, Zhongda Hospital, Medical School, Southeast University.
authors.forename: Shengda
authors.initials: S
authors.lastname: Hu
authors.forename: Gaoliang
authors.initials: G
authors.lastname: Yan
authors.forename: Hongzeng
authors.initials: H
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.forename: Genshan
authors.initials: G
authors.lastname: Ma
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1