RESUMEN
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.
Asunto(s)
Inhibidores de la Angiogénesis/metabolismo , Enfermedad de Chagas/etiología , Proteínas Protozoarias/metabolismo , Trypanosoma cruzi/metabolismo , Actinas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Línea Celular , Proliferación Celular , Enfermedad de Chagas/metabolismo , Enfermedad de Chagas/parasitología , Citoesqueleto/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Matriz Extracelular , Regulación de la Expresión Génica , Humanos , Ratones , Modelos Biológicos , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Multimerización de Proteína , Proteínas Protozoarias/farmacología , Receptores CXCR4 , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologíaRESUMEN
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.