Hypoxic Preconditioning Increases Survival of Cardiac Progenitor Cells via the Pim-1 Kinase-Mediated Anti-Apoptotic Effect

被引:31
|
作者
Hu, Shengda [1 ]
Yan, Gaoliang [1 ]
Xu, Hongzeng [1 ]
He, Wei [2 ]
Liu, Zhiyong [2 ]
Ma, Genshan [1 ]
机构
[1] Southeast Univ, Sch Med, Zhongda Hosp, Dept Cardiol, Nanjing 210009, Jiangsu, Peoples R China
[2] Southeast Univ, Sch Med, Zhongda Hosp, Dept Cardiothorac Surg, Nanjing 210009, Jiangsu, Peoples R China
关键词
Cardiac progenitor cells; Hypoxic; Mitochondria; Pim-1; Preconditioning; MESENCHYMAL STEM-CELLS; MYOCARDIAL-INFARCTION; CYTOCHROME-C; CARDIOMYOCYTE SURVIVAL; HEART; RELEASE; DIFFERENTIATION; REGENERATION; MITOCHONDRIA; ACTIVATION;
D O I
10.1253/circj.CJ-13-0841
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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). Methods and 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 6 h. 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) HPC4-l (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 mitochondria! 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.
引用
收藏
页码:724 / 731
页数:8
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