High-fat diet abolishes the cardioprotective effects of ischemic postconditioning in murine models despite increased thioredoxin-1 levels
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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.
KeywordsHigh-fat diet Thioredoxin Ischemic postconditioning Oxidative stress
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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