Cell Biochemistry and Biophysics

, Volume 69, Issue 1, pp 123–130 | Cite as

Hypercholesterolemia Abrogates the Cardioprotection of Ischemic Postconditioning in Isolated Rat Heart: Roles of Glycogen Synthase Kinase-3β and the Mitochondrial Permeability Transition Pore

  • Nan Wu
  • Xiaowen Zhang
  • Yuee Guan
  • Wenqi Shu
  • Pengyu Jia
  • Dalin Jia
Original Paper
First Online:

Abstract

Ischemic postconditioning (IPO) reduces lethal reperfusion injury under normal conditions, but its effectiveness in hypercholesterolemia (HC) is disputed. We measured the cardioprotection of IPO in hypercholesterolemic rats and determined the roles of glycogen synthase kinase-3β (GSK-3β) and the mitochondrial permeability transition pore (mPTP). Isolated rat hearts underwent 30-min global ischemia and 120-min reperfusion. Postconditioning protocol induced six cycles of 10s ischemia and 10s reperfusion at the onset of the reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride staining and cardiomyocyte apoptosis was assessed by TUNEL staining. GSK-3β phosphorylation was measured by immunoblotting. The opening of mPTP was measured by NAD+ content in myocardium. In normocholesterolemia (NC) groups, infarct size and cardiomyocyte apoptosis were significantly reduced after IPO. These reductions were completely abolished by HC, as evidenced by a similar infarct size and cardiomyocyte apoptosis observed between the IPO-HC and IR (ischemia–reperfusion)-HC groups. GSK-3β phosphorylation was significantly higher in the IPO-NC than the IPO-HC group. In addition, NAD+ content in myocardium, a marker of mPTP opening, was higher in the IPO-NC group than the IPO-HC group. In conclusion, cardioprotection of IPO is blocked by hypercholesterolemia. This might be due to the impairment of phosphorylation of GSK-3β and attenuation of mPTP opening.

Keywords

Ischemic postconditioning Hypercholesterolemia Glycogen synthase kinase-3β Mitochondrial permeability transition pore 
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Notes

Acknowledgments

These studies were supported by the Liaoning provincial science and technology projects, China (2009225051-1).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nan Wu
    • 1
  • Xiaowen Zhang
    • 2
  • Yuee Guan
    • 1
  • Wenqi Shu
    • 1
  • Pengyu Jia
    • 3
  • Dalin Jia
    • 1
  1. 1.Department of CardiologyThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Medical GeneticsChina Medical UniversityShenyangChina
  3. 3.China Medical UniversityShenyangChina

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