THE ROLE OF THIOREDOXIN 1 IN THE ISCHEMIC POSTCONDITIONING DURING EARLY STAGES OF ATHEROSCLEROSIS

TAMARA MAZO; VERÓNICA D´ANNUNZIO; TAMARA ZAOBORNYJ; VIRGINIA PEREZ; ANABELLA GOMEZ; GABRIELA BERG; MAGALI BARCHUK; GEORGINA OSSANI; MARÍA CARLA GRECO; MANUELA MARTINEFSKI; VALERIA TRIPODI; NESTOR LAGO; RICARDO J GELPI

Mar del Plata

Congreso; Reunion conjunta SAIC SAI SAFIS 2018; 2018

Sociedad Argentina de Investigación Clínica

Thioredoxin-1 (Trx1) has cardioprotective effects against ischemia/reperfusion (I/R) injury, and participates in ischemic postconditioning(PostC). However, whether Trx1 expression is altered and the PostCprotective effect is abolished during early stages of atheroscleroticdisease is unknown. The objective were evaluate whether a murinehigh-fat diet (HFD)-fed model that consistent with early stages ofatherosclerosis increased oxidative stress and consequently abolishedthe cardioprotection conferred by PostC. We used C57/BL6mice fed with control diet (CD) or HFD for 12 weeks. Isolated micehearts were subjected to 30min of ischemia and 120min of reperfusion(I/R group). For PostC group, after ischemia, six cycles ofR/I were performed (10sec per cycle) at the onset of reperfusion.We assessed infarct size and Trx1 expression. Also, we measuredoxidative stress by hydrogen peroxide (H2O2) production and levelsof reduced (GSH) and oxidized (GSSG) glutathione. We evaluetedmitochondrial function on state 3 and 4. In CD-PostC groupreduced infarct size (CD-I/R: 52.14 ± 2.8 vs. CD-PostC: 36.58 ±1.8, P< 0.05), and this cardioprotection was abolished in HFD-exposedmice. HFD increased H2O2 levels (CD: 0.91±0.09nmol/mgprotein vs. HFD: 1.27±0.15nmol/mg protein, P<0.05), produced ashift towards an oxidized intracellular environment (GSSG/GSH2),and increased Trx1 expression with higher fractions of oxidized protein(reduced Trx1/oxidized Trx1: HFD-Baseline 23% lower than inCD?Baseline). HFD fed mice had higher oxidized Trx1 levels andtherefore, when carrying out an I/R or PostC protocol, no significantchanges were observed among the groups (decreased reducedTrx1/oxidized Trx1: HFD-I/R: 29%; HFD-PostC: 31%). State 3 mitochondrialoxygen consumption in basal conditions decreased 24%in HFD-exposed mice and PostC improved state 3 values only in CDmice. We demonstrated that alterations in redox state at early stagesof atherosclerosis abolished cardioprotective induced by PostC,even with increased Trx1 levels.