Vascular Growth Factor Inhibition with Bevacizumab Improves Cardiac Electrical Alterations and Fibrosis in
Lindice Mitie Nisimura1, Roberto Rodrigues Ferreira1,2, Laura Lacerda Coelho1
1Laboratory of Innovations in Therapies, Education and Bioproducts, Oswaldo Cruz Institute (LITEB-IOC/Fiocruz), Oswaldo Cruz Foundation (Fiocruz), Av. Brasil, 4365, Manguinhos, Rio de Janeiro 21040-900, Brazil.
Insights
Inhibiting Vascular Endothelial Growth Factor A (VEGF-A) with bevacizumab improved survival and cardiac function in Chagas disease (CD) mouse models. This approach reduced inflammation and fibrosis, offering a potential new therapy for CD cardiomyopathy.
Area of Science:
- Cardiovascular Research
- Infectious Diseases
- Molecular Biology
Background:
- Chagas disease (CD), caused by *Trypanosoma cruzi*, is a leading cause of cardiomyopathy in endemic regions.
- Current treatments for CD focus on trypanocidal agents and managing cardiac symptoms, but lack options for progressive cardiac remodeling, inflammation, microvasculopathy, and fibrosis.
- Vascular Endothelial Growth Factor A (VEGF-A) plays a key role in angiogenesis and has been linked to fibrosis in chronic inflammatory conditions.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting the VEGF signaling pathway in a mouse model of Chagas disease.
- To determine the effects of bevacizumab, a monoclonal antibody targeting VEGF, on cardiac remodeling, function, and fibrosis in CD.
Main Methods:
- Swiss Webster mice were infected with the Y strain of *Trypanosoma cruzi*.
- Mice were treated with bevacizumab to inhibit VEGF signaling.
- Cardiac morphology, molecular markers, inflammation, angiogenesis, myofibroblast presence, and collagen levels were analyzed.
Main Results:
- Bevacizumab treatment significantly increased survival rates in infected mice.
- Inhibition of VEGF signaling reduced cardiac inflammation, improved electrical cardiac function, and diminished pathological angiogenesis.
- Bevacizumab decreased myofibroblast counts and restored normal collagen levels in cardiac tissue, indicating reduced fibrosis.
Conclusions:
- VEGF signaling is implicated in the development of cardiac microvasculopathy and fibrosis associated with Chagas disease.
- Inhibiting VEGF with bevacizumab demonstrates a promising therapeutic strategy for mitigating cardiac damage and improving outcomes in CD.
Abstract:
Chagas disease (CD) caused by Trypanosoma cruzi is a neglected illness and a major reason for cardiomyopathy in endemic areas. The existing therapy generally involves trypanocidal agents and therapies that control cardiac alterations. However, there is no treatment for the progressive cardiac remodeling that is characterized by inflammation, microvasculopathy and extensive fibrosis. Thus, the search for new therapeutic strategies aiming to inhibit the progression of cardiac injury and failure is necessary. Vascular Endothelial Growth Factor A (VEGF-A) is the most potent regulator of vasculogenesis and angiogenesis and has been implicated in inducing exacerbated angiogenesis and fibrosis in chronic inflammatory diseases. Since cardiac microvasculopathy in CD is also characterized by exacerbated angiogenesis, we investigated the effect of inhibition of the VEGF signaling pathway using a monoclonal antibody (bevacizumab) on cardiac remodeling and function. Swiss Webster mice were infected with Y strain, and cardiac morphological and molecular analyses were performed. We found that bevacizumab significantly increased survival, reduced inflammation, improved cardiac electrical function, diminished angiogenesis, decreased myofibroblasts in cardiac tissue and restored collagen levels. This work shows that VEGF is involved in cardiac microvasculopathy and fibrosis in CD and the inhibition of this factor could be a potential therapeutic strategy for CD.
