TRYPANOSOMA CRUZI PROMOTES VASCULAR ALTERATIONS ASSOCIATED WITH RISK OF CARDIOVASCULAR DISEASE

VOLPINI, XIMENA; BRUGO, BELEN; NATALI, LAUTARO; DE LA CRUZ-THEA, BENJAMÍN; MOTRAN, CRISTINA; MUSRI, MELINA M.

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. About 35% of infected patients develop the chronic phase of the diseases characterized by myocardiopathy, leading to cardiac failure and stroke. The rest of the patients remain asymptomatic (indetermined), although increased aorta stiffness (AS) has been described for these patients suggesting that the infection could contribute to vascular alterations. Despite the importance of the vasculature in regulating the homeostasis of the cardiovascular system, little is known about its changes in response to the infection. The aim of this work was to study vascular cell population changes during the acute phase of T. cruzi infection. Thoracic (Athor), abdominal aorta (Aabd), aortic arch, and brachiocephalic artery (BCA) were obtained from BALB/c mice infected with 500 tps of T. cruzi after 16 days post-infection with non-infected mice (NI) used as controls. Arterial segments were analyzed by multiparametric FACS followed by t-SNE analysis to identify different cell populations. Similar cell clusters were observed in BCA, Aabd, and arch but not in Athor of NI mice.. In addition, Athor was the segment presenting the major differences in cell cluster composition after infection. Thus, T. cruzi infection increased the percent of α-SMA+ cells (smooth muscle cells (SMC) marker), F4/80+ CD11b+ (macrophages, Mo), and the expression of markers of active immune cells. Interestingly, cell clusters co-expressing CML- and Mo-markers, which could indicate SMC-transdifferentiation into Mo or viceversa were also oberbed in Athor. Taken together, these results suggest that T. cruzi infection induces vascular changes, being Athor the segment most affected segment. Besides, transdifferentiation and immune cell activation could be mechanisms involved in these vascular alterations.