Trypanosoma cruzi Infection Promotes Vascular Remodeling and Coexpression of α-Smooth Muscle Actin and Macrophage Markers in Cells of the Aorta

VOLPINI, XIMENA; NATALI, LAUTARO; BRUGO, MARIA BELÉN; DE LA CRUZ-THEA, BENJAMIN; BAIGORRI, RUTH ELIANA; CERBÁN, FABIO MARCELO; FOZZATTI, LAURA; MOTRAN, CLAUDIA CRISTINA; MUSRI, MELINA MARA

ACS Infectious Diseases

American Chemical Society

Año: 2022

2373-8227

Chagas disease is an emerging global health problem; however, itremains neglected. Increased aortic stiffness (IAS), a predictor of cardiovascularevents, has recently been reported in asymptomatic chronic Chagas patients.After vascular injury, smooth muscle cells (SMCs) can undergo alterationsassociated with phenotypic switch and transdifferentiation, promoting vascularremodeling and IAS. By studying different mouse aortic segments, we tested thehypothesis that Trypanosoma cruzi infection promotes vascular remodeling.Interestingly, the thoracic aorta was the most affected by the infection.Decreased expression of SMC markers and increased expression of proliferativemarkers were observed in the arteries of acutely infected mice. In acutely andchronically infected mice, we observed cells coexpressing SMC and macrophage(Mo) markers in the media and adventitia layers of the aorta, indicating that T.cruzi might induce cellular processes associated with SMC transdifferentiationinto Mo-like cells or vice versa. In the adventitia, the Mo cell functional polarization was associated with an M2-like CD206+arginase-1+ phenotype despite the T. cruzi presence in the tissue. Only Mo-like cells in inflammatory foci were CD206+iNOS+. In addition tothe disorganization of elastic fibers, we found thickening of the aortic layers during the acute and chronic phases of the disease. Ourfindings indicate that T. cruzi infection induces a vascular remodeling with SMC dedifferentiation and increased cell populationscoexpressing α-SMA and Mo markers that could be associated with IAS promotion. These data highlight the importance of studyinglarge vessel homeostasis in Chagas disease.