Mechanisms of vascular dysfunction in acute phase of Trypanosoma cruzi infection in mice
| Autor: | Policarpo Sales-Junior, José Paulo da Silva, Steyner F. Cortes, Jader S. Cruz, Virginia S. Lemos, Luciano S. A. Capettini, Josiane F. Silva |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Trypanosoma cruzi Vasodilator Agents Nitric Oxide Synthase Type II Aorta Thoracic Nitric Oxide Receptors Thromboxane A2 Prostaglandin H2 Nitric oxide Contractility 03 medical and health sciences Thromboxane A2 chemistry.chemical_compound Superoxides Internal medicine parasitic diseases medicine Animals Chagas Disease Phosphorylation Pharmacology Dose-Response Relationship Drug biology Tumor Necrosis Factor-alpha Nitrotyrosine Transcription Factor RelA Endothelial Cells NADPH Oxidases Cytochrome b Group Mice Inbred C57BL Vasodilation Nitric oxide synthase Disease Models Animal 030104 developmental biology Endocrinology chemistry Cyclooxygenase 2 Host-Pathogen Interactions Immunology biology.protein Molecular Medicine Cyclooxygenase Thromboxane-A synthase Signal Transduction |
| Zdroj: | Vascular Pharmacology. 82:73-81 |
| ISSN: | 1537-1891 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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