Short Communication

Cardiovascular Drugs and Therapy

, Volume 21, Issue 6, pp 467-469

First online:

The Cardioprotective Effect of Necrostatin Requires the Cyclophilin-D Component of the Mitochondrial Permeability Transition Pore

  • S. Y. LimAffiliated withThe Hatter Cardiovascular Institute, University College London Hospital and Medical School
  • , S. M. DavidsonAffiliated withThe Hatter Cardiovascular Institute, University College London Hospital and Medical School
  • , M. M. MocanuAffiliated withThe Hatter Cardiovascular Institute, University College London Hospital and Medical School
  • , D. M. YellonAffiliated withThe Hatter Cardiovascular Institute, University College London Hospital and Medical School Email author 
  • , C. C. T. SmithAffiliated withThe Hatter Cardiovascular Institute, University College London Hospital and Medical School

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Abstract

Background

Necrostatin (Nec-1) protects against ischemia–reperfusion (IR) injury in both brain and heart. We have previously reported in this journal that necrostatin can delay opening of the mitochondrial permeability transition pore (MPTP) in isolated cardiomyocytes.

Aim

The aim of the present study was to investigate in more detail the role played by the MPTP in necrostatin-mediated cardioprotection employing mice lacking a key component of the MPTP, namely cyclophilin-D.

Method

Anaesthetized wild type (WT) and cyclophilin-D knockout (Cyp-D−/−) mice underwent an open-chest procedure involving 30 min of myocardial ischemia and 2 h of reperfusion, with subsequent infarct size assessed by triphenyltetrazolium staining. Nec-1, given at reperfusion, significantly limited infarct size in WT mice (17.7 ± 3% vs. 54.3 ± 3%, P < 0.05) but not in Cyp-D−/− mice (28.3 ± 7% vs. 30.8 ± 6%, P > 0.05).

Conclusion

The data obtained in Cyp-D−/− mice provide further evidence that Nec-1 protects against myocardial IR injury by modulating MPTP opening at reperfusion.

Key words

necrostatin mitochondrial permeability transition pore cyclophilin-D