Role of FAK signaling in chagasic cardiac hypertrophy
Cardiac hypertrophy and dysfunction are a significant complication of chronic Chagas disease, with heart failure, stroke, and sudden death related to disease progression. Thus, understanding the signaling pathways involved in the chagasic cardiac hypertrophy may provide potential targets for pharmac...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Brazilian Journal of Infectious Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1413867020301227 |
| _version_ | 1818191523773153280 |
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| author | Amanda R. Tucci Francisco O. R. de Oliveira, Jr Guilherme C. Lechuga Gabriel M. Oliveira Ana Carolina Eleuterio Liliane B. de Mesquita Priscila S.G. Farani Constança Britto Otacílio C. Moreira Mirian Claudia S. Pereira |
| author_facet | Amanda R. Tucci Francisco O. R. de Oliveira, Jr Guilherme C. Lechuga Gabriel M. Oliveira Ana Carolina Eleuterio Liliane B. de Mesquita Priscila S.G. Farani Constança Britto Otacílio C. Moreira Mirian Claudia S. Pereira |
| author_sort | Amanda R. Tucci |
| collection | DOAJ |
| description | Cardiac hypertrophy and dysfunction are a significant complication of chronic Chagas disease, with heart failure, stroke, and sudden death related to disease progression. Thus, understanding the signaling pathways involved in the chagasic cardiac hypertrophy may provide potential targets for pharmacological therapy. Herein, we investigated the implication of focal adhesion kinase (FAK) signaling pathway in triggering hypertrophic phenotype during acute and chronic T. cruzi infection. C57BL/6 mice infected with T. cruzi (Brazil strain) were evaluated for electrocardiographic (ECG) changes, plasma levels of endothelin-1 (ET-1) and activation of signaling pathways involved in cardiac hypertrophy, including FAK and ERK1/2, as well as expression of hypertrophy marker and components of the extracellular matrix in the different stages of T. cruzi infection (60–210 dpi). Heart dysfunction, evidenced by prolonged PR interval and decrease in heart rates in ECG tracing, was associated with high plasma ET-1 level, extracellular matrix remodeling and FAK signaling activation. Upregulation of both FAK tyrosine 397 (FAK-Y397) and serine 910 (FAK-S910) residues phosphorylation as well as ERK1/2 activation, lead to an enhancement of atrial natriuretic peptide gene expression in chronic infection. Our findings highlight FAK-ERK1/2 signaling as a regulator of cardiac hypertrophy in Trypanosoma cruzi infection. Both mechanical stress, induced by cardiac extracellular matrix (ECM) augment and cardiac overload, and ET-1 stimuli orchestrated FAK signaling activation with subsequent activation of the fetal cardiac gene program in the chronic phase of infection, highlighting FAK as an attractive target for Chagas disease therapy. |
| first_indexed | 2024-12-12T00:15:58Z |
| format | Article |
| id | doaj.art-9da849d447a04e92969afb4aa54b0657 |
| institution | Directory Open Access Journal |
| issn | 1413-8670 |
| language | English |
| last_indexed | 2024-12-12T00:15:58Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brazilian Journal of Infectious Diseases |
| spelling | doaj.art-9da849d447a04e92969afb4aa54b06572022-12-22T00:44:51ZengElsevierBrazilian Journal of Infectious Diseases1413-86702020-09-01245386397Role of FAK signaling in chagasic cardiac hypertrophyAmanda R. Tucci0Francisco O. R. de Oliveira, Jr1Guilherme C. Lechuga2Gabriel M. Oliveira3Ana Carolina Eleuterio4Liliane B. de Mesquita5Priscila S.G. Farani6Constança Britto7Otacílio C. Moreira8Mirian Claudia S. Pereira9Instituto Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Biologia Celular, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Fiocruz, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Fiocruz, Rio de Janeiro, RJ, Brazil; Corresponding author.Cardiac hypertrophy and dysfunction are a significant complication of chronic Chagas disease, with heart failure, stroke, and sudden death related to disease progression. Thus, understanding the signaling pathways involved in the chagasic cardiac hypertrophy may provide potential targets for pharmacological therapy. Herein, we investigated the implication of focal adhesion kinase (FAK) signaling pathway in triggering hypertrophic phenotype during acute and chronic T. cruzi infection. C57BL/6 mice infected with T. cruzi (Brazil strain) were evaluated for electrocardiographic (ECG) changes, plasma levels of endothelin-1 (ET-1) and activation of signaling pathways involved in cardiac hypertrophy, including FAK and ERK1/2, as well as expression of hypertrophy marker and components of the extracellular matrix in the different stages of T. cruzi infection (60–210 dpi). Heart dysfunction, evidenced by prolonged PR interval and decrease in heart rates in ECG tracing, was associated with high plasma ET-1 level, extracellular matrix remodeling and FAK signaling activation. Upregulation of both FAK tyrosine 397 (FAK-Y397) and serine 910 (FAK-S910) residues phosphorylation as well as ERK1/2 activation, lead to an enhancement of atrial natriuretic peptide gene expression in chronic infection. Our findings highlight FAK-ERK1/2 signaling as a regulator of cardiac hypertrophy in Trypanosoma cruzi infection. Both mechanical stress, induced by cardiac extracellular matrix (ECM) augment and cardiac overload, and ET-1 stimuli orchestrated FAK signaling activation with subsequent activation of the fetal cardiac gene program in the chronic phase of infection, highlighting FAK as an attractive target for Chagas disease therapy.http://www.sciencedirect.com/science/article/pii/S1413867020301227Chagas diseaseTrypanosoma cruziCardiac hypertrophyEndothelin-1FAK signaling |
| spellingShingle | Amanda R. Tucci Francisco O. R. de Oliveira, Jr Guilherme C. Lechuga Gabriel M. Oliveira Ana Carolina Eleuterio Liliane B. de Mesquita Priscila S.G. Farani Constança Britto Otacílio C. Moreira Mirian Claudia S. Pereira Role of FAK signaling in chagasic cardiac hypertrophy Brazilian Journal of Infectious Diseases Chagas disease Trypanosoma cruzi Cardiac hypertrophy Endothelin-1 FAK signaling |
| title | Role of FAK signaling in chagasic cardiac hypertrophy |
| title_full | Role of FAK signaling in chagasic cardiac hypertrophy |
| title_fullStr | Role of FAK signaling in chagasic cardiac hypertrophy |
| title_full_unstemmed | Role of FAK signaling in chagasic cardiac hypertrophy |
| title_short | Role of FAK signaling in chagasic cardiac hypertrophy |
| title_sort | role of fak signaling in chagasic cardiac hypertrophy |
| topic | Chagas disease Trypanosoma cruzi Cardiac hypertrophy Endothelin-1 FAK signaling |
| url | http://www.sciencedirect.com/science/article/pii/S1413867020301227 |
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