CHAGAS DISEASE IN OBESOGENIC CONTEXT: A HIGHLIGHT ROLE FOR VISCERAL ADIPOSE TISSUE AS A CHRONIC RESERVOIR OF TRYPANOSOMA CRUZI THAT CONTRIBUTES TO ASSOCIATED CARDIOVASCULAR COMPLICATIONST

BUENOS AIRES

Congreso; CONGRESS ON BIOSCIENCE; 2017

EVENTO CONJUNTO DE 10 SOCIEDADES CIENTÍFICAS ARGENTINAS

CHAGAS DISEASE IN AN OBESOGENIC CONTEXT: A HIGHLIGHT ROLE OF VISCERAL ADIPOSE TISSUE AS A CHRONIC RESERVOIR OF Trypanosoma cruzi THAT CONTRIBUTES TO ASSOCIATED CARDIOVASCULAR COMPLICATIONS Marìa E. Cabalén (1) Liliana Sanmarco (2), María F. Cabral (1), Natalia Eberhardt (2) Marta Andrada (1), Nicolás Ponce (2)), Susana Gea (2), Maria Pilar Aoki (2), Roxana C. Cano (1, 2), (1)Facultad de Ciencias Químicas, UA Área CS. AGR. ING. BIO Y S CONICET. Universidad Católica de Córdoba.(2)CIBICI-CONICET. Facultad de Ciencias Químicas, Universidad Nacional de Córdoba.Chagas disease and obesity are chronic and growing public health concerns with associated cardiovascular (CV) complications. Oxidative stress (OS) and inflammation are common pathophysiological mechanisms that predispose to CV events. We hypothesize that in an obesogenic context, Trypanosoma cruzi infection, may be a key player on the immune-metabolic dysregulation and on the development of CV complications. To elucidate this complex interrelation, we evaluate in our obesity and T. cruzi infection model the lipid and lipoprotein systemic changes as early CV biomarkers, and the oxidative and immune-inflammatory alterations in visceral adipose tissue (VAT). C57BL/6 wild type mice were divided in LFD (4% fat), DIO (14% fat/ 5% fructose), DIO+I and LFD+I groups, and studied for 24 weeks. Infection was done with 500 Tulahuèn parasites (i.p). Plasma triglycerides (TG), total cholesterol (TC) and apolipoprotein B100 (apoB100) levels were assessed by enzymatic kits and immunoturbidimetry. Lipoprotein patterns were analyzed by electrophoresis. In VAT, OS and CD36 receptor were evaluated by lipid peroxidation (malondyaldehyde, MDA) and W-B, respectively. Parasite load was determined in VAT and heart by q-PCR. AT macrophages (ATM) were characterized according to M1 (F4/80+CD11c+CD206-) or M2 (F4/80+CD11c-CD206+) phenotypes by flow cytometry. Although an improvement on TG and TC levels was seen on DIO+I compared to DIO mice (p<0.001; p<0.001), apoB100 levels were increased in all groups in relation to LFD (p< 0.05); suggesting the presence of atherogenic small and dense low density lipoprotein (LDL) particles in the infected groups. These were accompanied by qualitative differences in lipoprotein bands compared to LFD group. Significant decreases in the adiponectin levels were seen in both infected groups compared to DIO and LFD (p<0.001; p<0.001). In VAT, inflammatory cell-infiltration and OS were exacerbated in DIO+I compared to LFD+I mice (p<0.05). Also, total leukocytes were increased in DIO+I group (p<0.001). Despite a high number of ATM with an M2 phenotype was found on DIO+I versus LFD+I mice (p< 0,001), an increase in the CD36 expression was seen in DIO+I vs LFD+I (p<0.05). Interestingly, parasite load was significantly increased in VAT from DIO+I in comparison to LFD +I mice (p<0.05). Conversely in heart, a low parasite load was observed, highlighting VAT as a more suitable chronic reservoir. In an obesogenic and chronic infection context, VAT has a relevant role during chronic T. cruzi infection. The strong inflammatory and oxidative response is probably counter-balanced by the parasite, which may induce the polarization of ATM to a M2 phenotype to favor its own survival. Thus, parasite persistence would be a key trigger in the progression of vascular Chagas disease such as early atherosclerosis/ cardiomyopathy.