TRYPANOSOMA CRUZI INFECTION PROMOTES CELLULAR PROCESSES ASSOCIATED WITH AORTIC STIFFNESS

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

Congreso; Reunión conjunta de SAIC. SAI. AAFE. NANOMED; 2021

SAIC. SAI. AAFE. NANOMED

Chagas disease (CD), caused by Trypanosoma cruzi, affects 6million people worldwide. Recently, increased aortic stiffness (IAS)in CD patients classified as indeterminate without cardiac compli-cations was observed by sensitive imaging. IAS is a predictor ofcardiovascular disease (CVD) risk. Smooth muscle cells (SMC)phenotypic alteration during vascular injury is associated with re-duced elasticity, impaired distensibility, fibrosis, and IAS. The aimof this work was to evaluate SMC alterations associated with IASduring T. cruzi infection. Thoracic (Thor), abdominal aorta (Abd),and brachiocephalic artery (BCA) were obtained from both controlnon-infected (NI), and acute T. cruzi infected BALB/c mice (INF).RT-qPCR, immunofluorescence, and FACS revealed alterationsrelated to SMC phenotypic switch from a contractile to a syntheticstate in arteries of INF mice, with loss of SMC markers expressionsuch as α-SMA, calponin, transgelin, and Myh11. In addition, wefound increased expression of klf4, Ki67, and β-catenin which areassociated with SMC and macrophage (Mo) proliferation. Recently,it has been demonstrated that SMC can transdifferentiate into Mo-like cells. Mo functional phenotype in aortic segments was principal-ly M2-resident-like CD206+Arg-1+, despite T. cruzi presence. OnlyMo in inflammatory foci close to vasa vasorum of Thor from INFmice were CD206+iNOS+ . We used α-SMA+ and F4/80+CD11b+as SMC and Mo populations, respectively. We found α-SMA+ cellsF4/80+CD11b+, and viseversa, only in arteries from INF group. Us-ing confocal microscopy, we found cells co-expressing α-SMA+ andthe Mo marker CD68 in the media, and in the adventitia of INF mice.Our findings suggest that the infection induces SMC dedifferenti-ation and transdifferentiation associated with IAS promotion. Thisknowledge is important to review the integration of indeterminateCD patients on the risk list and comorbidities of CVD, and promoteeither preventive or therapeutic strategies.