Role of FAK signaling in chagasic cardiac hypertrophy
| Autor: | Liliane Batista de Mesquita, Gabriel Melo de Oliveira, Mirian Claudia de Souza Pereira, Amanda R. Tucci, Guilherme C. Lechuga, Priscila Silva Grijó Farani, Otacilio C. Moreira, Constança Britto, Ana Carolina Eleuterio, Francisco Odêncio Rodrigues de Oliveira |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
Chagas disease Trypanosoma cruzi lcsh:QR1-502 Cardiomegaly Sudden death lcsh:Microbiology Muscle hypertrophy lcsh:Infectious and parasitic diseases Focal adhesion 03 medical and health sciences Mice Atrial natriuretic peptide Medicine Animals lcsh:RC109-216 Phosphorylation 0303 health sciences Endothelin-1 030306 microbiology business.industry medicine.disease Mice Inbred C57BL Chronic infection Cardiac hypertrophy Infectious Diseases FAK signaling Heart failure Cancer research Signal transduction business Brazil Signal Transduction |
| Zdroj: | Brazilian Journal of Infectious Diseases, Vol 24, Iss 5, Pp 386-397 (2020) Brazilian Journal of Infectious Diseases v.24 n.5 2020 Brazilian Journal of Infectious Diseases Brazilian Society of Infectious Diseases (BSID) instacron:BSID Brazilian Journal of Infectious Diseases, Volume: 24, Issue: 5, Pages: 386-397, Published: 30 NOV 2020 |
| ISSN: | 1413-8670 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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