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High-fat diet abolishes the cardioprotective effects of ischemic postconditioning in murine models despite increased thioredoxin-1 levels.
- Source :
-
Molecular and cellular biochemistry [Mol Cell Biochem] 2019 Feb; Vol. 452 (1-2), pp. 153-166. Date of Electronic Publication: 2018 Aug 09. - Publication Year :
- 2019
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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/GSH <superscript>2</superscript> ), 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.
- Subjects :
- Animals
Male
Mice
Mice, Inbred C57BL
Mitochondria metabolism
Mitochondria pathology
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury pathology
Myocardial Reperfusion Injury prevention & control
Oxidation-Reduction
Diet, High-Fat adverse effects
Disease Models, Animal
Ischemic Postconditioning
Myocardial Reperfusion Injury etiology
Thioredoxins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4919
- Volume :
- 452
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30094601
- Full Text :
- https://doi.org/10.1007/s11010-018-3421-x