Renovascular hypertension increases serum TNF and CX3CL1 in experimental Trypanosoma cruzi infection.

M.C Silva,R.P Machado,D Coelho Junior,A.C Alzamora,P.M Martinelli,M.R Moura Junior,A Talvani,M.A Azevedo,V.P Figueiredo

doi:10.1590/1414-431x20186690

Abstract

Trypanosoma cruzi triggers a progressive inflammatory response affecting cardiovascular functions in humans and experimental models. Angiotensin II, a key effector of the renin-angiotensin system, plays roles in mediating hypertension, heart failure, and inflammatory responses. T. cruzi and AngII can induce inflammatory responses by releasing inflammatory mediators. The aim of this study was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats infected with T. cruzi. Our data showed an increase in serum AngII in uninfected and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham) animals. The baseline systolic blood pressure was higher in both uninfected and infected 2K1C rats. Despite no difference in circulating parasites in the acute phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post-infection in 2K1C rats in association with higher cardiac inflammatory infiltration. In summary, AngII-induced hypertension associated with T. cruzi infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat model, thereby intensifying cardiac inflammatory infiltration and worsening the underlying inflammation triggered by this protozoan.

Highlights

Trypanosoma cruzi is a flagellated protozoan whose membrane glycoproteins act as antigens capable of triggering an inflammatory response in mammalian hosts [1]
Arterial hypertension may positively modulate inflammation, which in turn controls circulating parasites, we observed no significant difference between parasitemia of 2K1C rats and Sham animals (Figure 1A)
We evaluated whether the co-occurrence of both diseases could interfere with the inflammatory, parasitological, and physiological pathways using the 2K1C arterial-hypertension model for Wistar rats infected with the Y-strain of T. cruzi

Summary

Introduction

Trypanosoma cruzi is a flagellated protozoan whose membrane glycoproteins act as antigens capable of triggering an inflammatory response in mammalian hosts [1] This immune-cell activation promotes the release of inflammatory mediators and antibodies that regulate parasite entry into the bloodstream. Because of its well-adapted escape mechanisms, the immune system typically fails and T. cruzi persists in muscle cells Once these parasites reach the cardiac cells, they trigger a local and persistent inflammatory response that is inevitably associated with cellular and tissue destruction [2]. Both human Chagas disease and experimental models of T. cruzi infection affect heart muscle, and promote endothelial dysfunction of systemic blood vessels [3,4]. This may eventually lead to cardiac fibrosis, which affects cardiac function, and the general health of the individual [6]

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