The late phase of ischemic preconditioning induces a prosurvival genetic program that results in marked attenuation of apoptosis

Adam B. Stein, Roberto Bolli, Yiru Guo, Ou Li Wang, Wei Tan, Wen Jian Wu, Xiaoping Zhu, Yanqing Zhu, Yu Ting Xuan

Research output: Contribution to journalArticle

Abstract

Although the cardioprotection afforded by the late phase of ischemic preconditioning (PC) in ischemia/reperfusion (I/R) injury has been well studied, it is unknown whether this beneficial effect can be attributed to inhibition of apoptosis. We hypothesized that ischemic PC affords protection by suppressing apoptosis and examined the underlying mechanisms. Myocardial infarction was produced in mice (30-min coronary occlusion). In animals preconditioned 24 h earlier with six 4-min coronary occlusion/4-min reperfusion (O/R) cycles, there was a marked decrease in apoptosis as assessed by three different parameters: hairpin-1 assay, caspase-3 activity, and immunohistochemical analysis of active caspase-3 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1). This protective effect was accompanied by increased expression of multiple antiapoptotic proteins that regulate both the mitochondria-mediated (Bcl-xL and Mcl-1) and the death-receptor-mediated (c-FLIPL and c-FLIPS) pathway of apoptosis and by decreased expression of the proapoptotic protein Bad. This is the first demonstration that the late phase of ischemic PC attenuates cardiac apoptosis after ischemia/reperfusion injury and that this salubrious effect is associated with a complex genetic prosurvival program that results in modulation of several key proteins involved in both the mitochondrial and the death receptor pathways of apoptosis.

Original languageEnglish (US)
Pages (from-to)1075-1085
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume42
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • Antiapoptotic protein
  • Apoptosis
  • Ischemia/reperfusion
  • Myocardial ischemia
  • Preconditioning

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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