TNF-α partially modulates the endothelial dysfunction during the acute phase of Trypanosoma cruzi infection

Whereas the effects of Trypanosoma cruzi (T. cruzi) infection are well-characterised in the heart, its impact on the vasculature has received little attention. In this study, we investigated the effects of acute and chronic T. cruzi infection on vascular responsiveness and the underlying mechanisms.

Male Wistar Hannover rats were infected intraperitoneally with 1 × 10⁵ trypomastigotes of the T. cruzi Y strain. Vascular function was evaluated in the thoracic aorta during the acute (9 days post-infection, dpi) and chronic (60 dpi) phases of infection.

No changes in vascular responsiveness were observed during the chronic phase. However, acute T. cruzi infection induced endothelial dysfunction, leading to vascular hypercontractility, although it did not alter the anti-contractile effect of perivascular adipose tissue (PVAT). Infected rats exhibited increased levels of TNF-α in the aorta, but not in the PVAT or serum. TNF-α inhibition with etanercept (1 mg·kg^-1·day^-1; i.p.) prevented both endothelial dysfunction and oxidative stress (upregulation of NOX2/superoxide [O₂•^-] generation), as well as the increase in thromboxane A₂ (TXA₂).

Our results demonstrate that TNF-α mediates vascular dysfunction during the acute phase of T. cruzi infection. Our results indicate that TNF-α contributes to endothelial dysfunction and vascular hypercontractility by promoting O₂•^- generation, upregulating NOX2 and increasing TXA₂ production. Although PVAT is not dysfunctional during acute infection, increased myeloperoxidase (MPO) activity was detected within it, suggesting it may act as a reservoir for neutrophils.