Vascular Growth Factor Inhibition with Bevacizumab Improves Cardiac Electrical Alterations and Fibrosis in Experimental Acute Chagas Disease

Simple Summary Chagas disease is an infectious condition caused by Trypanosoma cruzi that especially affects the heart; the infected patient may present alterations in heartbeat and an increase in heart volume. When the infection is not treated and remains active for a long time, it can lead to heart failure and death. In many cases, microscopic heart analysis reveals many defense cells that characterize inflammation and several scars in the organ-called fibrosis. Multiple components are involved in inflammation and fibrosis development; for example, an increased blood vessel number contributes to the process as it allows for a greater quantity of cell arrival. VEFG-A is a potent vessel formation inducer. In this context, we investigated the effect of inhibition of VEGF in T. cruzi-infected mice, and we found that the VEGF blockage significantly increased survival, reduced inflammation, improved cardiac electrical function, diminished the vessel formation and reduced cardiac fibrosis. This work shows that VEGF is involved in cardiac alterations observed in Chagas disease and the inhibition of this factor could be a potential treatment for T. cruzi-infected patients.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.