TRYPANOSOMA CRUZI INFECTION AS AN UNDERLYING FACTOR CATALYZING THE ONSET OF HEMODYNAMIC PERTURBATIONS AND CARDIOVASCULAR DISEASES

VOLPINI, X; QUIROZ, JN; HERRERA, MR; HELLRIEGEL, MF; BRUGO, MB; MUSRI, M; FOZZATTI, L; STEMPIN. CC; PEREZ, AR; MOTRAN, CC

San Luis

Congreso; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología.; 2023

Sociedad Argentina de Inmunología

According to the World Health Organization, cardiovascular diseases (CVD) arethe leading global cause of death. Chagas disease (CD), caused by Trypanosomacruzi (TC) infection, is considered the primary cause of death due to infectiouscardiomyopathy. Historically, seropositive patients without discernible symptomsof cardiomyopathy have been grouped under the "indeterminate" classification.This categorization has perpetuated the lack of care of ~70% of CD patients. Bythe measurement of the carotid-femoral pulse wave velocity (cf-PWV), recentresearch has unveiled that indeterminate patients manifest increased aorticstiffness (IAS), the primary risk indicator of developing CVD. To contribute to thecurrent extent of knowledge of TC infection as a factor in triggering CVD andhemodynamic disorders, we have evaluated “residual” hemodynamic andmetabolic risk factors in infected mice and CD-patients, respectively.To study hemodynamic risk factors associated with vessel alterations, Balb/c micewere infected with TC (Tulahuen strain), and the cell populations of thoracic,abdominal, and brachiocephalic aortic segments were analyzed by FACS atdifferent days post-infection (dpi), using uninfected mice as controls. In the acutephase of infection (18 dpi), TC induced increased frequency (%) of CD45+ CD3+(p<0.0001) and CD45+ CD11b+ (p<0.0001) cells. During both acute and chronic(60 dpi) phases, the infected group exhibited a significant increase of %CD45-αSMA+ population with high expression of αSMA+ (p<0.001). Interestingly, high α-SMA expression, an IAS- associated mechanism, was also found in CD45+ cells;particularly in CD45+ CD11b+ population during the acute phase (p<0.0001), andcorrelating with the % of CD45+ CD11b+ in the chronic (p<0.01).Finally, we focused towards residual metabolic risk factors linked to aorticstiffness. In this regard, we explored the plasma metabolic profile of CD patientsusing LC-MS. We compared the metabolic profiles between healthy donors andthree patient cohorts representing different degrees of CD severity (indeterminate,moderate- cardiomyopathy, or severe-cardiomyopathy). Thus, we identified IASassociatedmetabolites that could be potential candidates for differentialbiomarkers indicative of the cardiovascular and cardiac risk degree in patientswith the infection by TC. Taken together, our results support evidence that TCinfection may act as an underlying factor catalyzing the onset of hemodynamicperturbations and CVD. Considering that cf-PWV is the gold standarddetermination of IAS but currently it is only used in research, our findingspromote the importance of contemplating the evaluation of some residualmetabolites associated with cardiovascular risk in all TC- infected patients. Thiswould be critical to promote the opportunity to prevent cardiomyopathy, but alsohemodynamic alterations, and CVD among individuals affected by TC infection,particularly those categorized as “indeterminate”.