Trypanosoma cruzi P21: a potential novel target for chagasic cardiomyopathy therapy

Sci Rep. 2015 Nov 17:5:16877. doi: 10.1038/srep16877.

Abstract

Chagas disease, which is caused by the parasite Trypanosoma cruzi, is an important cause of cardiomyopathy in Latin America. It is estimated that 10%-30% of all infected individuals will acquire chronic chagasic cardiomyopathy (CCC). The etiology of CCC is multifactorial and involves parasite genotype, host genetic polymorphisms, immune response, signaling pathways and autoimmune progression. Herein we verified the impact of the recombinant form of P21 (rP21), a secreted T. cruzi protein involved in host cell invasion, on progression of inflammatory process in a polyester sponge-induced inflammation model. Results indicated that rP21 can recruit immune cells induce myeloperoxidase and IL-4 production and decrease blood vessels formation compared to controls in vitro and in vivo. In conclusion, T. cruzi P21 may be a potential target for the development of P21 antagonist compounds to treat chagasic cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / etiology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Chagas Disease / drug therapy
  • Chagas Disease / parasitology
  • Chagas Disease / pathology*
  • Chemotaxis / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Interleukin-4 / metabolism
  • Leukocytes / cytology
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects
  • Peroxidase / metabolism
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Trypanosoma cruzi / isolation & purification
  • Trypanosoma cruzi / metabolism*

Substances

  • Cytokines
  • Protozoan Proteins
  • Recombinant Proteins
  • Interleukin-4
  • Peroxidase