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Updated: Aug 20, 2025

Quantitative 3D Imaging of Trypanosoma cruzi-Infected Cells, Dormant Amastigotes, and T Cells in Intact Clarified Organs
Published on: June 23, 2022
Increased angiogenesis parallels cardiac tissue remodelling in experimental acute Trypanosoma cruzi infection
Lindice Mitie Nisimura1, Roberto Rodrigues Ferreira1,2, Laura Lacerda Coelho1
1Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Rio de Janeiro, RJ, Brasil.
Insights
Trypanosoma cruzi infection causes increased blood vessel growth (angiogenesis) in the heart during the acute phase of experimental Chagas disease (CD), alongside cardiac remodeling. This study clarifies the role of angiogenesis in CD physiopathology.
Area of Science:
- Cardiovascular Biology
- Parasitology
- Immunology
Background:
- Angiogenesis, or new blood vessel formation, is linked to tissue damage in noninfectious diseases.
- The role of angiogenesis in the physiopathology of Chagas disease (CD) remains largely unknown.
Purpose of the Study:
- To investigate the impact of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD.
- To explore the signaling pathways involved in blood vessel formation and cardiac remodeling in response to T. cruzi infection.
Main Methods:
- Evaluation of signaling pathways in Swiss Webster mice infected with the Y strain of T. cruzi.
- Analysis of angiogenesis-related molecules (VEGF-A, Flk-1, pERK, HIF-1α, CD31, α-SMA) and blood vessel growth.
- Histopathological, immunohistochemical, and Western blot analyses of cardiac tissue.
Main Results:
- Acute T. cruzi infection induced exacerbated cardiac angiogenesis and remodeling in mice.
- Increased levels of HIF-1α, VEGF-A, Flk-1, and pERK were observed in infected hearts.
- Elevated α-SMA+ cells, collagen deposition, and angiogenesis were noted in the cardiac tissue of infected mice.
Conclusions:
- Cardiac angiogenesis during acute experimental T. cruzi infection is associated with cardiac inflammation and remodeling.
- The findings highlight the role of angiogenesis in the acute phase of Chagas disease.
Background:
Angiogenesis has been implicated in tissue injury in several noninfectious diseases, but its role in Chagas disease (CD) physiopathology is unclear.
Objectives:
The present study aimed to investigate the effect of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD.
Methods:
The signalling pathway involved in blood vessel formation and cardiac remodelling was evaluated in Swiss Webster mice infected with the Y strain of T. cruzi. The levels of molecules involved in the regulation of angiogenesis, such as vascular endothelial growth factor-A (VEGF-A), Flk-1, phosphorylated extracellular-signal-regulated protein kinase (pERK), hypoxia-inducible factor-1α (HIF-1α), CD31, α-smooth muscle actin (α-SMA) and also the blood vessel growth were analysed during T. cruzi infection. Hearts were analysed using conventional histopathology, immunohistochemistry and western blotting.
Findings:
In this study, our data demonstrate that T. cruzi acute infection in mice induces exacerbated angiogenesis in the heart and parallels cardiac remodelling. In comparison with noninfected controls, the cardiac tissue of T. cruzi-infected mice presented higher levels of (i) HIF-1α, VEGF-A, Flk-1 and pERK; (ii) angiogenesis; (iii) α-SMA+ cells in the tissue; and (iv) collagen -1 deposition around blood vessels and infiltrating throughout the myocardium.
Main Conclusions:
We observed cardiac angiogenesis during acute experimental T. cruzi infection parallels cardiac inflammation and remodelling.
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