The role of thioredoxin 1 in the ischemicpostconditioning on mice fed high fat diet

TAMARA MAZO; ANABELLA GOMEZ; TAMARA ZAOBORNYJ; VIRGINIA PEREZ; ELIANA CICALE; VERÓNICA CASANOVA; MAGALI BARCHUK; GABRIELA BERG; VERÓNICA D´ANNUNZIO; RICARDO J GELPI

CABA

Congreso; Joint meeting of bioscience societies. LXII Annual meeting of argentine society of clinical investigation (SAIC); 2017

Sociedad Argentina de Investigación Clínica

Thioredoxin-1 (Trx1) has cardioprotective effects against ischemia/reperfusion (I/R) injury, and participates in mechanisms mediatingischemic postconditioning (PostC). It remains unclear whether the PostC protective effects are exerted during initial stages of atheroscleroticdisease by alteringTrx1 expression. The objective of thisstudy was to generate a murine high-fat diet (HFD) fed model thatdeveloped phenotypes consistent with early-stage atherosclerosis,and then evaluate increased oxidative stress, altered mitochondrialbioenergetics and Trx1 expression in the HFD model. Ultimately, themodel was used to determine whether HFD exposure abolished thecardioprotection conferred by PostC. C57/BL6 mice were fed withcontrol diet (CD) or HFD for 12 weeks. Mice isolated hearts was subjectedto 30 min of ischemia and 120 min of reperfusion (I/R group).For PostC subjects, after ischemia, six cycles were performed ofreperfusion/ischemia (10 sec respectively, per cycle) at the onsetof reperfusion. Data are expressed as mean±SEM and p<0.05 wasconsidered statistically significant. n= 6 each group. In CD group,the Post had reduced infarct size (CD-I/R: 52.14±2.8 vs. CD-PostC:36.58±1.8, P<0.05). This cardioprotection was abolished in HFD-exposedsubjects. HFD increased production of hydrogen peroxideand Trx1 expression. State 3 mitochondrial oxygen consumptionin basal conditions was 24% decreased in HFD-exposed subjects.PostC restored state 3 values in controls more completely than inHFD-exposed subjects. Redox states and mitochondrial bioenergeticswere altered in HFD-exposed subjects, leading to increasedTrx1levels. These changes were accompanied by failed cardioprotectionin HFD-subjects that is normally conferred by PostC. In conclusion,this study demonstrated the novel finding that alterations in redoxstate were enough to abolished cardioprotective mechanisms, suchas those induced by PostC.