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

Sci Rep. 2017 Mar 21:7:44978. doi: 10.1038/srep44978.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Angiogenesis Inhibitors / metabolism*
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Cell Line
  • Cell Proliferation
  • Chagas Disease / etiology*
  • Chagas Disease / metabolism
  • Chagas Disease / parasitology
  • Cytoskeleton / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Extracellular Matrix
  • Gene Expression Regulation
  • Humans
  • Mice
  • Models, Biological
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Protein Multimerization
  • Protozoan Proteins / metabolism*
  • Protozoan Proteins / pharmacology
  • Receptors, CXCR4
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Trypanosoma cruzi / metabolism*

Substances

  • Actins
  • Angiogenesis Inhibitors
  • CXCR4 protein, human
  • Protozoan Proteins
  • Receptors, CXCR4
  • Recombinant Proteins