Arrhythmogenic mechanisms in right heart diseases

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

Abstract

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)

Scientific publications

(18)

(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)

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. (14/09861-1, 19/21304-4)

JOVIANO-SANTOS, JULLIANE VASCONCELOS; SANTOS-MIRANDA, ARTUR; ROMAN-CAMPOS, DANILO. Cardiac electrical remodeling and neurodegenerative diseases association. Life Sciences, v. 267, FEB 15 2021. (19/21304-4, 18/22830-9, 18/20777-3, 14/09861-1)

GILMARA BEATRIZ ANDRADE DA SILVA; DIEGO SANTOS SOUZA; JOSÉ EVALDO RODRIGUES MENEZES-FILHO; JÚLIO ALVES DA SILVA-NETO; JADER DOS SANTOS CRUZ; DANILO R. ROMAN-CAMPOS; LUCINDO JOSÉ QUINTANS-JÚNIOR; CARLA MARIA LINS DE VASCONCELOS. A (-)-Carvona Modula a Sinalização de Cálcio Intracelular com Ação Antiarrítmica em Corações de Ratos. Arquivos Brasileiros de Cardiologia, v. 119, n. 2, p. 294-304, 2022-08-05. (19/21304-4, 19/18918-0)

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. (19/21304-4, 18/20777-3, 18/22830-9)

SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; COSTA, ALEXANDRE DANTAS; CRUZ, JADER SANTOS; RHANA, PAULA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE VASCONCELOS; DURCO, AIMEE OBOLARI; LINS VASCONCELOS, CARLA MARIA; ROMAN-CAMPOS, DANILO. Experimental hypothyroidism induces cardiac arrhythmias and ranolazine reverts and prevents the phenotype. Life Sciences, v. 308, p. 13-pg., 2022-09-13. (20/14635-1, 21/05584-7, 19/21304-4, 19/18918-0)

ROMAN-CAMPOS, DANILO; SALES-JUNIOR, POLICARPO; COSTA, ALEXANDRE D.; SOUZA, DIEGO SANTOS; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE, V; ROPERT, CATHERINE; CRUZ, JADER S.. Impact of IFN-gamma Deficiency on the Cardiomyocyte Function in the First Stage of Experimental Chagas Disease. MICROORGANISMS, v. 10, n. 2, p. 7-pg., 2022-02-01. (19/18918-0, 18/22830-9, 19/21304-4, 18/20777-3)

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. (14/09861-1, 19/21304-4, 18/22830-9, 18/20777-3)

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; et al. 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. (19/21304-4, 19/18918-0)

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. (18/22830-9, 18/20777-3, 19/21304-4)

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. (19/21304-4, 14/09861-1, 18/20777-3)

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. (19/21304-4, 14/09861-1, 18/20777-3, 18/22830-9, 20/09403-4)

SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, V. JULLIANE; CRUZ-NASCIMENTO, TAYNARA; NERI, ELIDA ADALGISA; SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; KRIEGER, JOSE E.; ROMAN-CAMPOS, DANILO. The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine heart and human cardiomyocytes derived from induced pluripotent stem cells. Toxicology Letters, v. 359, p. 10-pg., 2022-04-15. (18/22830-9, 19/18918-0, 21/05584-7, 19/21304-4, 20/14635-1, 18/20777-3)

RHANA, PAULA; BARROS, GUILHERME MENDES; SANTOS, VINICIUS CISNEIROS DE OLIVEIRA; COSTA, ALEXANDRE DANTAS; DOS SANTOS, DANILLO MENEZES; FERNANDES-BRAGA, WESLLEY; DURCO, AIMEE OBOLARI; SANTOS, MARCIO ROBERTO VIANA; ROMAN-CAMPOS, DANILO; DE VASCONCELOS, CARLA MARIA LINS; et al. S-limonene protects the heart in an experimental model of myocardial infarction induced by isoproterenol: Possible involvement of mitochondrial reactive oxygen species. European Journal of Pharmacology, v. 930, p. 11-pg., 2022-07-18. (19/18918-0, 19/21304-4)

DA SILVA, MARIA VITORIA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE, V; SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; SARMENTO, JAQUELINE OLIVEIRA; BESERRA, SAMUEL SANTOS; ROMAN-CAMPOS, DANILO. The insecticide beta-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype. Clinical Science, v. 136, n. 5, p. 15-pg., 2022-03-01. (21/05584-7, 19/18918-0, 18/20777-3, 18/22830-9, 20/09403-4, 19/21304-4)

TEIXEIRA-FONSECA, JORGE LUCAS; JOVIANO-SANTOS, JULLIANE V.; BESERRA, SAMUEL SANTOS; CONCEICAO, MICHAEL RAMON DE LIMA; LEAL-SILVA, POLYANA; MARQUES, LEISIANE PEREIRA; SOUZA, DIEGO SANTOS; ROMAN-CAMPOS, DANILO. Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. N/A, p. 14-pg., 2023-06-20. (19/21304-4, 19/18918-0, 21/15122-0, 20/14635-1, 21/05584-7)

JORGE LUCAS TEIXEIRA-FONSECA; JULLIANE VASCONCELOS JOVIANO-SANTOS; FABIANA DA SILVA ALCÂNTARA; POLYANA LEAL DA SILVA; MICHAEL RAMON LIMA CONCEIÇÃO; DANILO ROMAN-CAMPOS. Estudo Morfofuncional do Átrio Esquerdo Isolado de um Modelo Experimental de Hipertensão Pulmonar em Ratos. Arquivos Brasileiros de Cardiologia, v. 120, n. 10, 2023-10-20. (19/21304-4, 21/05584-7)

DA SILVA, AGATHA RIBEIRO; NERI, ELIDE A.; TURACA, LAURO THIAGO; DARIOLLI, RAFAEL; FONSECA-ALANIZ, MIRIAM H.; SANTOS-MIRANDA, ARTUR; ROMAN-CAMPOS, DANILO; VENTURINI, GABRIELA; KRIEGER, JOSE E.. NOTCH1 is critical for fibroblast-mediated induction of cardiomyocyte specialization into ventricular conduction system-like cells in vitro. SCIENTIFIC REPORTS, v. 10, n. 1, p. 18-pg., 2020-09-30. (19/21304-4, 14/24577-8, 18/22830-9, 15/50216-5, 17/05829-4, 13/17368-0, 14/09861-1)

TEIXEIRA-FONSECA, JORGE LUCAS; DE LIMA CONCEICAO, MICHAEL RAMON; LEAL-SILVA, POLYANA; ROMAN-CAMPOS, DANILO. Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline-induced pulmonary hypertension. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. 132, n. 5, p. 10-pg., 2023-03-01. (19/21304-4, 21/05584-7)