Laboratório de Tripanosomatídeos, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, MG, Brasil.
Laboratório de Bioquímica e Toxinas Animais, Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, MG, Brasil.
Sci Rep. 2017 Mar 21;7:44978. doi: 10.1038/srep44978.
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.
慢性恰加斯心脏病（CCC）是由细胞内原生动物克氏锥虫引起的恰加斯病最重要的形式；据估计，10-30%的慢性患者会出现这种临床表现。CCC 最常见和最严重的形式可能与心室异常有关，如心力衰竭、心律失常、心脏阻滞、血栓栓塞事件和猝死。因此，在这项研究中，我们提出评估一种名为 P21（rP21）的克氏锥虫重组蛋白的抗血管生成活性，以及天然蛋白对 CCC 的潜在影响。我们的数据表明，rP21 的抗血管生成活性取决于该蛋白与 CXCR4 受体的直接相互作用。这种能力可能与肌动蛋白和血管生成相关基因表达的调节有关。因此，我们的结果表明，克氏锥虫 P21 是开发针对 CCC 的创新治疗药物的有吸引力的靶标。
