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Published on: November 5, 2021
Trypanosoma cruzi P21: a potential novel target for chagasic cardiomyopathy therapy
Thaise Lara Teixeira1, Fabrício Castro Machado1,2, Aline Alves da Silva1
1Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, MG, Brasil.
Insights
Trypanosoma cruzi P21 protein (rP21) promotes inflammation by recruiting immune cells and increasing myeloperoxidase and IL-4. Targeting rP21 may offer a new strategy for treating chagasic cardiomyopathy.
Area of Science:
- Immunology
- Parasitology
- Cardiology
Background:
- Chagas disease, caused by Trypanosoma cruzi, is a leading cause of cardiomyopathy in Latin America.
- Chronic chagasic cardiomyopathy (CCC) affects 10%-30% of infected individuals, with complex etiology.
- Understanding T. cruzi's role in CCC pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of recombinant P21 (rP21), a secreted T. cruzi protein, on inflammatory processes.
- To evaluate rP21's effect on immune cell recruitment, inflammatory markers, and angiogenesis.
- To explore the potential of targeting rP21 for CCC treatment.
Main Methods:
- Utilized a polyester sponge-induced inflammation model in vitro and in vivo.
- Assessed immune cell infiltration, myeloperoxidase activity, and IL-4 production.
- Quantified blood vessel formation (angiogenesis) in response to rP21.
Main Results:
- Recombinant P21 (rP21) demonstrated the ability to recruit immune cells.
- rP21 induced increased myeloperoxidase and IL-4 production.
- A decrease in blood vessel formation was observed in the presence of rP21 compared to controls.
Conclusions:
- T. cruzi P21 protein influences the inflammatory response in a model system.
- rP21's pro-inflammatory effects suggest its involvement in Chagas disease progression.
- P21 antagonists could be a potential therapeutic strategy for chagasic cardiomyopathy.
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.
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