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Molecular and Cellular Biochemistry

, Volume 452, Issue 1–2, pp 153–166 | Cite as

High-fat diet abolishes the cardioprotective effects of ischemic postconditioning in murine models despite increased thioredoxin-1 levels

  • Tamara Mazo
  • Verónica D´Annunzio
  • Tamara Zaobornyj
  • Virginia Perez
  • Anabella Gomez
  • Gabriela Berg
  • Magali Barchuk
  • Georgina Ossani
  • Manuela Martinefski
  • Valeria Tripodi
  • Néstor Lago
  • Ricardo J. GelpiEmail author
Article
  • 54 Downloads

Abstract

Ischemic postconditioning (PostC) reduces infarct size in healthy experimental models. However, if protective effects of PostC are abolished during early stages of atherosclerotic and if this is related with a disbalance in mitochondrial energetics and alterations in thioredoxin-1 (Trx1) is still unknown. The objectives were to generate a murine high-fat diet (HFD)-fed model that developed in a phenotype consistent with early stages of atherosclerosis to then evaluate whether HFD exposure increased oxidative stress and consequently abolished the cardioprotection conferred by PostC. We used C57/BL6 mice fed with control diet (CD) or HFD for 12 weeks. Isolated mice hearts were subjected to 30 min of ischemia and 120 min of reperfusion (I/R group). For PostC group, after ischemia, six cycles of reperfusion/ischemia were performed (10 s per cycle) at the onset of reperfusion. In CD group, the PostC reduced infarct size (CD-I/R: 52.14 ± 2.8 vs. CD-PostC: 36.58 ± 1.8, P < 0.05) and increased phosphorylation of GSK3β (CD-PostC: 2.341 ± 1.03 vs. CD-Baseline: 0.923 ± 0.41 AUOD, P < 0.05), and this cardioprotection was abolished in HFD-exposed mice. HFD increased hydrogen peroxide levels, produced a shift towards an oxidized intracellular environment (GSSG/GSH2), and increased Trx1 expression with higher fractions of oxidized protein. State 3 mitochondrial oxygen consumption in basal conditions decreased 24% in HFD-exposed mice and PostC improved state 3 values only in CD mice. Cellular redox state and mitochondrial bioenergetics were altered in HFD-exposed mice. We demonstrated that alterations in redox state at early stages of atherosclerosis abolished cardioprotective mechanisms, such as those induced by PostC, even with increased Trx1 levels.

Keywords

High-fat diet Thioredoxin Ischemic postconditioning Oxidative stress 

Notes

Acknowledgements

This study was supported by the University of Buenos Aires (UBACYT# 20020110100159); and the National Agency for Technological and Scientific Promotion (PICT 0373) and CONICET (PIP 2014/0012).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tamara Mazo
    • 1
    • 3
  • Verónica D´Annunzio
    • 1
    • 3
  • Tamara Zaobornyj
    • 2
  • Virginia Perez
    • 1
    • 3
  • Anabella Gomez
    • 1
    • 3
  • Gabriela Berg
    • 4
  • Magali Barchuk
    • 4
  • Georgina Ossani
    • 5
  • Manuela Martinefski
    • 6
  • Valeria Tripodi
    • 6
  • Néstor Lago
    • 5
  • Ricardo J. Gelpi
    • 1
    • 3
    Email author
  1. 1.Department of Pathology, Faculty of Medicine, Institute of Cardiovascular PhysiopathologyUniversity of Buenos AiresBuenos AiresArgentina
  2. 2.School of Pharmacy and Biochemistry, Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET)University of Buenos AiresBuenos AiresArgentina
  3. 3.Faculty of Medicine, Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET)University of Buenos AiresBuenos AiresArgentina
  4. 4.Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos AiresArgentina
  5. 5.Department of Pathology, Faculty of MedicineUniversity of Buenos Aires, Experimental and Applied Pathology CenterBuenos AiresArgentina
  6. 6.Department of Pharmaceutics Technology, School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos AiresArgentina

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