REFERENCES

01.

de Araújo-Jorge TC, Waghabi MC, Hasslocher-Moreno AM, Xavier S, Higuchi MDL, Keramidas M, et al. Implication of transforming growth factor-b 1 in Chagas disease myocardiopathy. J Infect Dis. 2002; 186: 1823-8.

PubMed

02.

de Andrade JP, Marin Neto JA, de Paola AAV, Vilas-Boas F, Oliveira GMM, Bacal F, et al. I Latin American guidelines for the diagnosis and treatment of Chagas cardiomyopathy. Arq Bras Cardiol. 2011; 97: 1-48.

PubMed

03.

Massagué J. TGF? s ignalling i n c ontext. Nat R ev Mol C ell Biol. 2012; 13: 616-30.

PubMed

04.

Ferreira RR, Waghabi MC, Bailly S, Feige JJ, Hasslocher-Moreno AM, Saraiva RM, et al. Chagas disease immunogenetics and the search for disease biomarkers: insights from TGF-beta studies. Front Cell Infect Microbiol. 2021; doi: 10.3389/fcimb.2021.767576.

PubMed

05.

de Araújo-Jorge TC, Waghabi MC, Bailly S, Feige J. The TGF-? pathway as an emerging target for Chagas disease therapy. Clin Pharmacol Ther. 2012; 92: 613-21.

PubMed

06.

Saraiva RM, Waghabi MC, Vilela MF, Madeira FS, da Silva GMS, Xavier SS, et al. Predictive value of transforming growth factor-?1 in Chagas disease: towards a biomarker surrogate of clinical outcome. Trans R Soc Trop Med Hyg. 2013; 107: 518-25.

PubMed

07.

Nogueira LG, Frade AF, Ianni BM, Laugier L, Pissetti CW, Cabantous S, et al. Functional IL18 polymorphism and susceptibility to chronic Chagas disease. Cytokine 2015; 73(1): 79-83.

PubMed

08.

Calzada JE, Beraun Y, Gonzalez CI, Mart?n J. Cytokine transforming growth factor beta 1 (TGF b 1) gene polymorphisms and Chagas disease susceptibility in Peruvian and Colombian patients. Cytokine. 2009; 45: 149-53.

PubMed

09.

Ferreira FF, Madeira FS, Alves GF, Chambela MC, Vaz Curvo EO, Moreira AS, et el. TGF-? polymorphisms are a risk fator for Chagas disease. Dis Markers. 2018; 2018: 4579198.

PubMed

10.

Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type ?1. Hum Mol Genet. 1999; 8(1): 93-7.

PubMed

11.

Anderton MJ, Mellor HR, Bell A, Sadler C, Pass M, Powell S, et al. Induction of heart valve lesions by small-molecule ALK5 inhibitors. Toxicol Pathol. 2011; 39(6): 916-24.

PubMed

12.

Waghabi MC, de Souza EM, de Oliveira GM, Keramidas M, Feige J, de Araújo-Jorge TC, et al. Pharmacological inhibition of transforming growth factor beta signaling decreases infection and prevents heart damage in acute Chagas’ disease. Antimicrob Agents Chemother. 2009; 53: 4694-4701.

PubMed

13.

de Oliveira FL, Souza EM, de Oliveira GM, de Araújo-Jorge, TC, Degrave WM, Feige J, et al. Oral administration of GW788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in Chagas disease. PLoS Negl Trop Dis. 2012; 6: e1696.

PubMed

14.

Cutrullis RA, Poklepovich TJ, Postan M, Freilij HL, Petray PB. Immunomodulatory and anti-fibrotic effects of ganglioside therapy on the cardiac chronic form of experimental Trypanosoma cruzi infection. Int Immunopharmacol. 2011; 11(8): 1024-31.

PubMed

15.

Ferreira RR, Abreu RS, Vilar-Pereira G, Degrave W, Meuser-Batista M, Ferreira NVC, et al. TGF-? inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a preclinical study of chronic Chagas’ heart disease. PLoS Negl Trop Dis. 2019; 13(7): e0007602.

PubMed

16.

Chen Y, Lüttmann FF, Schoger E, Schöler HR, Zelarayán LC, Kim KP, et al. Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice. Science. 2021; 373(6562): 1537-40.

PubMed

17.

Fernández-Ruiz I. Rejuvenating cardiomyocytes facilitates heart regeneration. Nat Rev Cardiol. 2021; 18: 807.

PubMed

Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 117 | 2022

Perspective

Transforming growth factor-? as a therapeutic target for the cardiac damage of Chagas disease

Mariana Caldas Waghabi^1,+, Roberto Rodrigues Ferreira^1,4, Rayane da Silva Abreu¹, Wim Degrave¹, Elen Mello de Souza², Sabine Bailly³, Jean-Jacques Feige³, Tania C de Araújo-Jorge⁴

¹Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil
²Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular, Rio de Janeiro, RJ, Brasil
³Institut National de la Santé et de la Recherche Médicale, Biology of Cancer and Infection Laboratory, Grenoble, France
⁴Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Rio de Janeiro, RJ, Brasil

DOI: 10.1590/0074-02760210395

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ABSTRACT

Transforming growth factor beta (TGF-?) is deeply involved on the pathogenesis of Chagas disease. Our group has been investigating the participation of this pleiotropic cytokine in different aspects of Chagas disease over the last 20 years. Important observations have been made, such as: (i) the ability of Trypanosoma cruzi in activating latent TGF-?; (ii) the potential involvement of TGF-? pathway on T. cruzi invasion of host cells; (iii) association of TGF-? with parasite intracellular replication; (iv) cardiac fibrosis development and maintenance; (v) disruption of Connexin-43 plaque structures and (vi) inflammation and immune response. In this perspective article we intend to discuss the advances of the potential use of new therapies targeting TGF-? to treat the cardiac alterations of Chagas disease-affected patients.

key words: transforming growth factor beta therapeutic target damage Chagas disease cardiac

REFERENCES

01. de Araújo-Jorge TC, Waghabi MC, Hasslocher-Moreno AM, Xavier S, Higuchi MDL, Keramidas M, et al. Implication of transforming growth factor-b 1 in Chagas disease myocardiopathy. J Infect Dis. 2002; 186: 1823-8.

PubMed

02. de Andrade JP, Marin Neto JA, de Paola AAV, Vilas-Boas F, Oliveira GMM, Bacal F, et al. I Latin American guidelines for the diagnosis and treatment of Chagas cardiomyopathy. Arq Bras Cardiol. 2011; 97: 1-48.

PubMed

03. Massagué J. TGF? s ignalling i n c ontext. Nat R ev Mol C ell Biol. 2012; 13: 616-30.

PubMed

04. Ferreira RR, Waghabi MC, Bailly S, Feige JJ, Hasslocher-Moreno AM, Saraiva RM, et al. Chagas disease immunogenetics and the search for disease biomarkers: insights from TGF-beta studies. Front Cell Infect Microbiol. 2021; doi: 10.3389/fcimb.2021.767576.

PubMed

05. de Araújo-Jorge TC, Waghabi MC, Bailly S, Feige J. The TGF-? pathway as an emerging target for Chagas disease therapy. Clin Pharmacol Ther. 2012; 92: 613-21.

PubMed

06. Saraiva RM, Waghabi MC, Vilela MF, Madeira FS, da Silva GMS, Xavier SS, et al. Predictive value of transforming growth factor-?1 in Chagas disease: towards a biomarker surrogate of clinical outcome. Trans R Soc Trop Med Hyg. 2013; 107: 518-25.

PubMed

07. Nogueira LG, Frade AF, Ianni BM, Laugier L, Pissetti CW, Cabantous S, et al. Functional IL18 polymorphism and susceptibility to chronic Chagas disease. Cytokine 2015; 73(1): 79-83.

PubMed

08. Calzada JE, Beraun Y, Gonzalez CI, Mart?n J. Cytokine transforming growth factor beta 1 (TGF b 1) gene polymorphisms and Chagas disease susceptibility in Peruvian and Colombian patients. Cytokine. 2009; 45: 149-53.

PubMed

09. Ferreira FF, Madeira FS, Alves GF, Chambela MC, Vaz Curvo EO, Moreira AS, et el. TGF-? polymorphisms are a risk fator for Chagas disease. Dis Markers. 2018; 2018: 4579198.

PubMed

10. Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type ?1. Hum Mol Genet. 1999; 8(1): 93-7.

PubMed

11. Anderton MJ, Mellor HR, Bell A, Sadler C, Pass M, Powell S, et al. Induction of heart valve lesions by small-molecule ALK5 inhibitors. Toxicol Pathol. 2011; 39(6): 916-24.

PubMed

12. Waghabi MC, de Souza EM, de Oliveira GM, Keramidas M, Feige J, de Araújo-Jorge TC, et al. Pharmacological inhibition of transforming growth factor beta signaling decreases infection and prevents heart damage in acute Chagas’ disease. Antimicrob Agents Chemother. 2009; 53: 4694-4701.

PubMed

13. de Oliveira FL, Souza EM, de Oliveira GM, de Araújo-Jorge, TC, Degrave WM, Feige J, et al. Oral administration of GW788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in Chagas disease. PLoS Negl Trop Dis. 2012; 6: e1696.

PubMed

14. Cutrullis RA, Poklepovich TJ, Postan M, Freilij HL, Petray PB. Immunomodulatory and anti-fibrotic effects of ganglioside therapy on the cardiac chronic form of experimental Trypanosoma cruzi infection. Int Immunopharmacol. 2011; 11(8): 1024-31.

PubMed

15. Ferreira RR, Abreu RS, Vilar-Pereira G, Degrave W, Meuser-Batista M, Ferreira NVC, et al. TGF-? inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a preclinical study of chronic Chagas’ heart disease. PLoS Negl Trop Dis. 2019; 13(7): e0007602.

PubMed

16. Chen Y, Lüttmann FF, Schoger E, Schöler HR, Zelarayán LC, Kim KP, et al. Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice. Science. 2021; 373(6562): 1537-40.

PubMed

17. Fernández-Ruiz I. Rejuvenating cardiomyocytes facilitates heart regeneration. Nat Rev Cardiol. 2021; 18: 807.

PubMed

+ Corresponding author: mariana@ioc.fiocruz.br
ORCID https://orcid.org/0000-0002-1205-9507
Received 17 December 2021
Accepted 20 December 2021

Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 117 | 2022

Perspective

Transforming growth factor-? as a therapeutic target for the cardiac damage of Chagas disease

Mariana Caldas Waghabi^1,+, Roberto Rodrigues Ferreira^1,4, Rayane da Silva Abreu¹, Wim Degrave¹, Elen Mello de Souza², Sabine Bailly³, Jean-Jacques Feige³, Tania C de Araújo-Jorge⁴

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Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 117 | 2022

Perspective

Transforming growth factor-? as a therapeutic target for the cardiac damage of Chagas disease

Mariana Caldas Waghabi1,+, Roberto Rodrigues Ferreira1,4, Rayane da Silva Abreu1, Wim Degrave1, Elen Mello de Souza2, Sabine Bailly3, Jean-Jacques Feige3, Tania C de Araújo-Jorge4

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Mariana Caldas Waghabi^1,+, Roberto Rodrigues Ferreira^1,4, Rayane da Silva Abreu¹, Wim Degrave¹, Elen Mello de Souza², Sabine Bailly³, Jean-Jacques Feige³, Tania C de Araújo-Jorge⁴