Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy

克氏锥虫蛋白 21 的抗血管生成活性的机制见解及其对恰加斯心肌病发病的潜在影响

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作者:Samuel Cota Teixeira, Daiana Silva Lopes, Sarah Natalie Cirilo Gimenes, Thaise Lara Teixeira, Marcelo Santos da Silva, Rebecca Tavares E Silva Brígido, Felipe Andrés Cordero da Luz, Aline Alves da Silva, Makswell Almeida Silva, Pilar Veras Florentino, Paula Cristina Brígido Tavares, Marlus Alves Dos

Abstract

Chronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoan Trypanosoma cruzi; it is estimated that 10-30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein from T. cruzi named P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein's direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate that T. cruzi P21 is an attractive target for the development of innovative therapeutic agents against CCC.

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