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Circulation Journal
Vol. 78 (2014) No. 3 724-731

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http://doi.org/10.1253/circj.CJ-13-0841

Regenerative Medicine

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 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.  (Circ J 2014; 78: 724–731)

Copyright © 2014 THE JAPANESE CIRCULATION SOCIETY

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