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Abstract:

Trypanosoma cruzi infection induces an intense inflammatory response in diverse host tissues. The immune response and the microvascular abnormalities associated with infection are crucial aspects in the generation of heart damage in Chagas disease. Upon parasite uptake, macrophages, which are involved in the clearance of infection, increase inflammatory mediators, leading to parasite killing. The exacerbation of the inflammatory response may lead to tissue damage. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent nuclear transcription factor that exerts important anti-inflammatory effects and is involved in improving endothelial functions and proangiogenic capacities. In this study, we evaluated the intermolecular interaction between PPARγ and a new synthetic PPARγ ligand, HP24, using virtual docking. Also, we showed that early treatment with HP24, decreases the expression of NOS2, a pro-inflammatory mediator, and stimulates proangiogenic mediators (vascular endothelial growth factor A, CD31, and Arginase I) both in macrophages and in the heart of T. cruzi-infected mice. Moreover, HP24 reduces the inflammatory response, cardiac fibrosis and the levels of inflammatory cytokines (TNF-α, interleukin 6) released by macrophages of T. cruzi-infected mice. We consider that PPARγ agonists might be useful as coadjuvants of the antiparasitic treatment of Chagas disease, to delay, reverse, or preclude the onset of heart damage. © 2017 Penas, Carta, Dmytrenko, Mirkin, Modenutti, Cevey, Rada, Ferlin, Sales and Goren.

Registro:

Documento: Artículo
Título:Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice
Autor:Penas, F.N.; Carta, D.; Dmytrenko, G.; Mirkin, G.A.; Modenutti, C.P.; Cevey, A.C.; Rada, M.J.; Ferlin, M.G.; Sales, M.E.; Goren, N.B.
Filiación:Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), CONICET, Buenos Aires, Argentina
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
Centro de Estudios Farmacológicos y Botánicos (CEFyBO)-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales (IQUIBICEN)-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina
Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Buenos Aires, Argentina
Palabras clave:Angiogenesis; Inflammatory mediators, heart fibrosis; Macrophages; New peroxisome proliferator-activated receptor gamma agonist; Trypanosoma cruzi; 3 hydroxy 1 methylpyridin 1 Ium 4 carboxylate; arginase 1; CD31 antigen; inducible nitric oxide synthase; interleukin 6; peroxisome proliferator activated receptor gamma; picolinic acid; tumor necrosis factor; unclassified drug; vasculotropin A; angiogenesis; animal cell; animal experiment; animal model; animal tissue; Article; body weight; Chagas disease; controlled study; enzyme linked immunosorbent assay; heart muscle fibrosis; histopathology; inflammation; macrophage; molecular docking; mouse; nonhuman; parasitemia; protein expression; protein structure; real time polymerase chain reaction; reverse transcription polymerase chain reaction; survival rate; Trypanosoma cruzi; Western blotting
Año:2017
Volumen:8
Número:DEC
DOI: http://dx.doi.org/10.3389/fimmu.2017.01738
Título revista:Frontiers in Immunology
Título revista abreviado:Front. Immunol.
ISSN:16643224
CAS:inducible nitric oxide synthase, 501433-35-8; picolinic acid, 3198-27-4, 98-98-6, 88161-53-9; vasculotropin A, 489395-96-2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16643224_v8_nDEC_p_Penas

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Citas:

---------- APA ----------
Penas, F.N., Carta, D., Dmytrenko, G., Mirkin, G.A., Modenutti, C.P., Cevey, A.C., Rada, M.J.,..., Goren, N.B. (2017) . Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice. Frontiers in Immunology, 8(DEC).
http://dx.doi.org/10.3389/fimmu.2017.01738
---------- CHICAGO ----------
Penas, F.N., Carta, D., Dmytrenko, G., Mirkin, G.A., Modenutti, C.P., Cevey, A.C., et al. "Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice" . Frontiers in Immunology 8, no. DEC (2017).
http://dx.doi.org/10.3389/fimmu.2017.01738
---------- MLA ----------
Penas, F.N., Carta, D., Dmytrenko, G., Mirkin, G.A., Modenutti, C.P., Cevey, A.C., et al. "Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice" . Frontiers in Immunology, vol. 8, no. DEC, 2017.
http://dx.doi.org/10.3389/fimmu.2017.01738
---------- VANCOUVER ----------
Penas, F.N., Carta, D., Dmytrenko, G., Mirkin, G.A., Modenutti, C.P., Cevey, A.C., et al. Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice. Front. Immunol. 2017;8(DEC).
http://dx.doi.org/10.3389/fimmu.2017.01738