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

Abstract

Chagas disease is an emerging global health problem; however, it remains neglected. Increased aortic stiffness (IAS), a predictor of cardiovascular events, has recently been reported in asymptomatic chronic Chagas patients. After vascular injury, smooth muscle cells (SMCs) can undergo alterations associated with phenotypic switch and transdifferentiation, promoting vascular remodeling and IAS. By studying different mouse aortic segments, we tested the hypothesis 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 proliferative markers were observed in the arteries of acutely infected mice. In acutely and chronically 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 transdifferentiation into 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 to the disorganization of elastic fibers, we found thickening of the aortic layers during the acute and chronic phases of the disease. Our findings indicate that T. cruzi infection induces a vascular remodeling with SMC dedifferentiation and increased cell populations coexpressing α-SMA and Mo markers that could be associated with IAS promotion. These data highlight the importance of studying large vessel homeostasis in Chagas disease.

Emodin Inhibits the Indoxyl Sulfate-Induced trans-Differentiation of Vascular Smooth Muscle Cells through Upregulating Thrombospondin-1

“…The gene and protein levels of α-SMA were downregulated in VSMCs differentiated into atherosclerosis phenotype induced by oxidative stress [ 26 ]. Therefore, among various trans -differentiation markers, α-SMA is considered an excellent marker for the phenotype transition and trans -differentiation of VSMCs [ 27 , 28 ]. In this study, the expression of α-SMA was closely related with TSP-1, which means that TSP-1 plays a key role in VSMCs phenotype maintenance.…”