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.
机构:
San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Mohsin, Sadia
Khan, Mohsin
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Khan, Mohsin
Nguyen, Jonathan
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Nguyen, Jonathan
Alkatib, Monique
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Alkatib, Monique
Siddiqi, Sailay
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Siddiqi, Sailay
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Hariharan, Nirmala
Wallach, Kathleen
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Wallach, Kathleen
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Monsanto, Megan
Gude, Natalie
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Gude, Natalie
Dembitsky, Walter
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Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
Dembitsky, Walter
Sussman, Mark A.
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San Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
San Diego State Univ, Dept Biol, San Diego, CA 92182 USASan Diego State Univ, San Diego Heart Res Inst, San Diego, CA 92182 USA
机构:
San Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USASan Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USA
Sundararaman, Balaji
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Avitabile, Daniele
Konstandin, Mathias H.
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San Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USASan Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USA
Konstandin, Mathias H.
Cottage, Christopher T.
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San Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USASan Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USA
Cottage, Christopher T.
Gude, Natalie
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San Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USASan Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USA
Gude, Natalie
Sussman, Mark A.
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San Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USASan Diego State Univ, SDSU Heart Inst & Biol Dept, San Diego, CA 92182 USA
机构:
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,Russia
RomanKholodenko
IrinaKholodenko
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Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,Russia
IrinaKholodenko
Viktor Sorokin
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机构:
Russian State Medical University,Ostrovityanova 1,Moscow 117312,RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,Russia
Viktor Sorokin
AnnaTolmazova
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机构:
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,Russia
AnnaTolmazova
OlgaSazonova
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机构:
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,Russia
OlgaSazonova
AntonBuzdin
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机构:
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry,16/10 Miklukho-Maklaya,Moscow 117997,Russia