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
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 involv...
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todo:paper_16643224_v8_nDEC_p_Penas2023-10-03T16:29:07Z 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 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. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_16643224_v8_nDEC_p_Penas |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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. 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Penas, F.N. |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| url |
http://hdl.handle.net/20.500.12110/paper_16643224_v8_nDEC_p_Penas |
| work_keys_str_mv |
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1807315607730782208 |