Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: The role of Bcl-2 family proteins and ERK1/2

Antigone Lazou, E. K. Iliodromitis, D. Cieslak, K. Voskarides, S. Mousikos, E. Bofilis, D. T. Kremastinos

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study aimed first, to examine whether short mechanical stretch with acute pressure overload (MPC), which has been shown to reduce infarct size after ischemia/reperfusion, mimics IPC in attenuating myocardial apoptosis and second, to evaluate whether induced cardioprotection involves modulation of the expression of the Bcl-2 family proteins and phosphorylation of prosurvival kinases. Methods and Results: A model of anaesthetized rabbit was used and the preconditioning protocol included one cycle of short ischemia/reperfusion, or short mechanical stretch with acute pressure overload. Preconditioning stimuli were equally effective in reducing the infarct size, determined after 4 h reperfusion. However, IPC but not MPC attenuated myocardial apoptosis. IPC restored the decreased expression of Bcl-2 and Bcl-xL observed in hearts subjected to ischemia and reperfusion only. Bax levels were not different among the groups. ERK1/2 were activated during reperfusion in both IPC and MPC groups. Conclusions: The data provide further evidence that apoptosis and necrosis contribute independently to infarct size after ischemia and reperfusion. Inhibition of the myocardial apoptotic processes by IPC may involve modulation of the expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL. ERK1/2 may be involved in the inhibition of both apoptosis and necrosis.

Original languageEnglish
Pages (from-to)2195-2204
Number of pages10
JournalApoptosis
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2 family
  • ERK1/2
  • Infarct size
  • Ischemia/reperfusion
  • Preconditioning
  • Rabbit heart

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