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Cardiovascular Pharmacology

Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells

Abstract

Aim:

Mesenchymal stem cells (MSC) are a promising candidate for cardiac replacement therapies. However, the majority of transplanted MSC are readily lost after transplantation because of poor blood supply, ischemia-reperfusion, and inflammatory factors. We aimed to study the effects of hypoxia preconditioning (HPC) on hypoxia/reoxygenation-induced apoptosis of MSC.

Methods:

Three generations of MSC were divided into 6 groups, including the normal group, hypoxia-reoxygenation (H/R) group, cyclosporine A (CsA), and the HPC 10 min, 20 min, and 30 min groups. The apoptotic index, cell viability, mitochondrial membrane potential, translocation of Bcl-2 and bax, extracellular regulated kinase (ERK), Akt, hypoxia-inducible factor 1-α, and the vascular endothelial growth factor (VEGF) were tested after H/R treatment.

Results:

HPC decreased the apoptotic index and increased the viability induced by H/R. Moreover, HPC markedly stabilized mitochondrial membrane potential, upregulated Bcl-2 and VEGF expressions, and increased the phosphorylation of ERK and Akt. As a positive control, CsA has the same function as HPC, except for promoting ERK and Akt phosphorylation and upregulating VEGF.

Conclusion:

HPC had a protective effect against MSC apoptosis induced by H/R via stabilizing mitochondrial membrane potential, upregulating Bcl-2 and VEGF, and promoting ERK and Akt phosphorylation. HPC has implications for the development of novel stem cell protective strategies.

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Correspondence to Jian-an Wang.

Additional information

This work was partly supported by grants from the National Natural Science Foundation of China (No 30670868) and a grant from the Zhejiang province Natural Science Foundation (No R206007).

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Wang, Ja., Chen, Tl., Jiang, J. et al. Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells. Acta Pharmacol Sin 29, 74–82 (2008). https://doi.org/10.1111/j.1745-7254.2008.00716.x

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Keywords

  • mesenchymal stem cells
  • apoptosis
  • hypoxia preconditioning
  • mitochondrial transmembrane potential
  • Bcl-2
  • extracellular regulated kinase1/2
  • Akt
  • vascular endothelial growth factor

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