Mechanisms of vascular dysfunction in acute phase of Trypanosoma cruzi infection in mice

Abstract

Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. Immunodetection of T. cruzi antigen TcRBP28 was observed in endothelial cells. There was a decreased endothelial nitric oxide synthase (eNOS)-derived NO-dependent vascular relaxation, and increased vascular contractility accompanied by augmented superoxide anions production. Endothelial removal, inhibition of cyclooxygenase 2 (COX-2), blockade of thromboxane A2 (TXA2) TP receptors, and scavenger of superoxide normalized the contractile response. COX-2, thromboxane synthase, inducible nitric oxide synthase (iNOS), p65 NFκB subunit and p22(phox) of NAD(P)H oxidase (NOX) subunit expressions were increased in vessels of chagasic animals. Serum TNF-α was augmented. Basal NO production, and nitrotyrosine residue expression were increased. It is concluded that T. cruzi invades mice aorta endothelial cells and increases TXA2/TP receptor/NOX-derived superoxide formation. Alongside, T. cruzi promotes systemic TNF-α increase, which stimulates iNOS expression in vessels and nitrosative stress. In light of the heart failure that develops in the chronic phase of the disease, to understand the mechanism involved in the increased contractility of the aorta is crucial.

Obesity, Inflammation, and Exercise Training: Relative Contribution of iNOS and eNOS in the Modulation of Vascular Function in the Mouse Aorta

“…NO and superoxide production in the aorta was measured using fluorescent dyes: 4-amino-5-methylamino-2′, 7′-difluorescein diacetate (DAF-FM; 8 μM; Invitrogen, USA) and dihydroethidium (DHE; 5 μM; Invitrogen), respectively (Silva et al, 2016). Aortic rings were embedded in a freezing medium to obtain transverse sections (10 μm).…”

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

“…Binding of TXA2 and TP activates a variety of cell types including dendritic cells, monocytes, platelets, cardiac myocytes and endothelial cells, resulting in apoptosis of cells, vasoconstriction, dilated cardiomyopathy, enhanced platelet adherence and aggregation ( Ashton et al, 2007 ). The TXA2 receptor antagonist SQ29548 has been shown to inhibit T. cruzi infection mediated through TP ( Ashton et al, 2007 ; Silva et al, 2016 ).…”

Curcumin exerts anti-inflammatory and vasoprotective effects through amelioration of NFAT-dependent endothelin-1 production in mice with acute Chagas cardiomyopathy

“…Cardiovascular production of vasoactive mediators has been implicated in the pathogenesis of the vasculopathy seen in Chagas myocarditis. 4 One of the most relevant vasculitis-promoting factors triggered by T. cruzi infection is endothelin-1 (ET-1). Much of the evidence suggests that this 21-amino acid peptide, produced by cardiac and endothelial cells among others, plays a pivotal role in the development of Chagas heart disease.…”