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Arrhythmogenic mechanisms in right heart diseases

Grant number: 19/21304-4
Support type:Regular Research Grants
Duration: September 01, 2020 - August 31, 2022
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Danilo Roman Campos
Grantee:Danilo Roman Campos
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers: Jader dos Santos Cruz ; Leda Quercia Vieira ; Manoel de Arcisio Miranda Filho ; Marcela Sorelli Carneiro Ramos


Cardiac arrhythmia due to right heart disease is an independent predictor of death. The etiology of heart disease is known to impact therapeutic choice. Right-sided heart disease may occur from direct injury to the heart tissue, or from changing in the right heart afterload leading to later cardiac remodeling. For both types of cardiac arrhythmias due to injury of the right side of the heart, neglected diseases that affect the Brazilian population are found, e.g. schistosomiasis and Chagas disease. In the context of schistosomiasis, one of the leading causes of death is cardiac arrhythmias derived from pulmonary arterial hypertension (PAH). There is evidence that arrhythmias derived from the right side of the heart are important in this context. In order to mimic the cardiovascular aspects found in schistosomiasis, we are going to use monocrotaline to induce PAH in rats. In this animal model, we are going to study the role of pH-sensitive potassium current in atrial arrhythmias. Considering Chagasic cardiomyopathy, it is already known that it changes the inflammatory state of the heart tissue, culminating in left as well as right ventricular injury. The Ca2 + / Calmodulin / Calmodulin kinase II (CAMKII) signaling axis is known to show greater activity in healthy right ventricular tissue when compared to the left one. Additionally, in chagasic cardiomyopathy increases the oxidative state of cardiac tissue, which favors the CAMKII pathway activation. Therefore, we are going to take advantage of our murine model of Chagas disease to study the CAMKII pathway in right and left ventricular cells in healthy and infected animals to determinate the relative contribution of CAMKII pathway to cellular excitability for the left and right side of the heart during Chagas disease. At the end of our project, we can propose new therapeutic approaches according to the etiology of the right heart disease. (AU)

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEIXEIRA-FONSECA, JORGE LUCAS; SANTOS-MIRANDA, ARTUR; DA SILVA, JOAB BARBOSA; MARQUES, LEISIANE PEREIRA; JOVIANO-SANTOS, JULLIANE VASCONCELOS; CHAVES NUNES, PAULA IDMA; ROMAN-CAMPOS, DANILO; SANTANA GONDIM, ANTONIO NEI. Eugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias. Life Sciences, v. 282, OCT 1 2021. Web of Science Citations: 0.
SANTOS-MIRANDA, ARTUR; COSTA, ALEXANDRE D.; JOVIANO-SANTOS, V, JULLIANE; RHANA, PAULA; BRUNO, ALEXANDRE SANTOS; ROCHA, PETER; CAU, STEFANY BRUNO; VIEIRA, LEDA Q.; CRUZ, JADER S.; ROMAN-CAMPOS, DANILO. Inhibition of calcium/calmodulin (Ca2+/CaM)-Calcium/calmodulin-dependent protein kinase II (CaMKII) axis reduces in vitro and ex vivo arrhythmias in experimental Chagas disease. FASEB JOURNAL, v. 35, n. 10 OCT 2021. Web of Science Citations: 0.
ELASORU, SEYI ELIJAH; RHANA, PAULA; DE OLIVEIRA BARRETO, TATIANE; DE SOUZA, DAYANE LORENA NAVES; MENEZES-FILHO, JOSE EVALDO RODRIGUES; SOUZA, DIEGO SANTOS; MOREIRA, MATHEUS VILARDO LOES; CAMPOS, MARCO TULIO GOMES; ADEDOSU, OLANIYI TEMITOPE; ROMAN-CAMPOS, DANILO; MELO, MARILIA MARTINS; CRUZ, JADER SANTOS. Andrographolide protects against isoproterenol-induced myocardial infarction in rats through inhibition of L-type Ca2+ and increase of cardiac transient outward K+ currents. European Journal of Pharmacology, v. 906, SEP 5 2021. Web of Science Citations: 0.
JOVIANO-SANTOS, V, J.; SANTOS-MIRANDA, A.; NERI, E. A.; FONSECA-ALANIZ, M. H.; KRIEGER, J. E.; PEREIRA, A. C.; ROMAN-CAMPOS, D. SCN5A compound heterozygosity mutation in Brugada syndrome: Functional consequences and the implication for pharmacological treatment. Life Sciences, v. 278, AUG 1 2021. Web of Science Citations: 0.
SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE V.; SARMENTO, JAQUELINE O.; COSTA, ALEXANDRE D.; SOARES, ALLYSSON T. C.; MACHADO, FABIANA S.; CRUZ, JADER S.; ROMAN-CAMPOS, DANILO. A novel substrate for arrhythmias in Chagas disease. PLoS Neglected Tropical Diseases, v. 15, n. 6 JUN 2021. Web of Science Citations: 0.
JOVIANO-SANTOS, JULLIANE VASCONCELOS; SANTOS-MIRANDA, ARTUR; ROMAN-CAMPOS, DANILO. Cardiac electrical remodeling and neurodegenerative diseases association. Life Sciences, v. 267, FEB 15 2021. Web of Science Citations: 0.
ROMAN-CAMPOS, DANILO; SALES-JUNIOR, POLICARPO; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, V, JULLIANE; ROPERT, CATHERINE; CRUZ, JADER S. Deletion of inducible nitric oxide synthase delays the onset of cardiomyocyte electrical remodeling in experimental Chagas disease. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1866, n. 12 DEC 1 2020. Web of Science Citations: 0.
S. BESERRA, SAMUEL; ROMAN-CAMPOS, DANILO. Impact of pacing frequency in amiodarone interaction with cardiomyocytes near physiological temperature in health and disease conditions. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. 128, n. 4 NOV 2020. Web of Science Citations: 0.

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