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

GOMEZ, ANABELLA; MAZO T; PEREZ, VIRGINIA; ZAOBORNYJ, TAMARA; BERG, GABRIELA; BARCHUK, MAGALI; D'ANNUNZIO V; GELPI RJ

Buenos Aires

Congreso; IV International Congress in Translational Medicine; 2018

Ischemic Postconditioning(IP) reduces infarct size in healthy experimental models. On the other hand, it has been exposed thatdyslipidemia could abolish the infarct size reduction conferred by IP caused byreactive oxygen species damage related to ischemia/reperfusion (I/R) injury. Nevertheless,it has not been shown whether the lack of protection by IP is related tothioredoxin 1 system (Trx1). Therefore, the aim was to evaluate if IP exertscardioprotective effect on dyslipidemic mice and determine if this lack ofreduction of infarct size is related to changes in mitochondrial bioenergeticsand Trx1 expression. C57/BL6 males?mice were used, fed with control diet (CD) or high-fat diet (HFD) during 12weeks. We measured clinicalbiochemistry parameters and the hearts were subjected to 30min of I and 120minR (Langendorff) (Group I/R n=7) or an IP protocol (n=7, 30min I, 6 Cycles of R/I10sec each and 120min R). We assessed ventricular function, infarct size and Trx1expression (n=6 per group). Also, we measured oxidative stress by H2O2production and mitochondrial oxygen consumption on state 3 and 4 (n=5 per group).In HFD mice total cholesterol, LDL and HDL increased compared to CD, buttriglycerides did not change. The behavior of ventricular function was similarin all the groups. In CD-IP the infarct size decreased compared to I/R group (I/R:55.2±2.6vsPI:40.2±1.6p=0.05). However, the cardioprotection was abolished in HFD mice (I/R:67.0±4.0vs.IP:61.0±4.2). In HFD not only H202 production (42%) but also Trx1expression (2.5-fold) increased; and State 3 mitochondrial oxygen consumptionin basal conditions decreased 24% respect to CD. We conclude that in HFD micethere is an alteration of the redox state and the mitochondrial bioenergeticsenough to trigger the endogenous antioxidant response. These changes wereaccompanied by the lack of protection by IP in HFD mice, even though Trx1levels has been increased.