Evaluation of the influence of fibroblasts on maturation and induction of cardiomyocytes with arrhythmogenic potential

• Grant number: 17/05829-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2017
• End date: March 31, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: José Eduardo Krieger
• Grantee: Agatha Ribeiro da Silva
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther, AP.TEM

Abstract

Cardiovascular diseases are currently the leading causes of death in the world. Transplants of stem cells and stem cell-derived cardiomyocytes have been used in the study of cell therapy as a form of regeneration and cardiac repair. However, stem cell-derived cardiomyocytes have immature characteristics regarding the contractile capacity and the conduction of action potentials, besides being related to the emergence of arrhythmias after cell transplantation.During my undergraduate research, we observed that cardiac fibroblasts increase the expression of the transcription factors Nkx2.5 and Gata-4, the expression of the connexins-40 and 43, and alter the profile of intracellular calcium handling in cardiomyocytes. Our data, together with the literature, support the hypothesis that fibroblasts play a role in the induction of rapidly conducting cells, which are characteristic of the ventricular conduction system, and this process may be directly related to the emergence of post-transplant arrhythmias in myocardial infarction models.In order to test this hypothesis, as well as propose strategies to improve the efficiency of cell therapies for heart disease, we will use human iPS-derived cardiomyocytes and human cardiac fibroblasts. We will standardize different cell cultures and co-cultures to evaluate the interaction of cardiomyocytes and fibroblasts, as well as to inhibit and select arrhythmogenic cells, by generating knockdown / knockout for Nkx2.5 / Irx3 and FACS Sorting for Connexin- 40, respectively. Therefore, the main goal of the present project is to evaluate the influence of fibroblasts on the maturation and induction of cardiomyocytes with arrhythmogenic potential. (AU)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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)

MIYAKAWA, AYUMI AUREA; BONIN, THAIZ FERRAZ; GASTALHO CAMPOS, LUCIENE CRISTINA; GIRAO-SILVA, THAIS; RIBEIRO-SILVA, JOAO CARLOS; OLIVEIRA DALLAN, LUIS ALBERTO; KRIEGER, JOSE EDUARDO. Activation of Interleukin-1 Beta in Arterialized Vein Grafts and the Influence of the -511C/T IL-1 beta Gene Polymorphism. JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE, v. 6, n. 2, JUN 2019. (17/05829-4, 13/17368-0)

MIYAKAWA, AYUMI AUREA; BASSANEZE, VINICIUS; DUARTE, NUBIA ESTEBAN; GIRAO-SILVA, THAIS; BIZERRA, MONICA NUNES; CAMPOS, JULLIANA CARVALHO; KRIEGER, JOSE EDUARDO. Temporal Change of Extracellular Matrix during Vein Arterialization Remodeling in Rats. JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE, v. 6, n. 1, MAR 2019. (17/05829-4, 13/17368-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Agatha Ribeiro da. Evaluation of the influence of fibroblasts on the maturation and induction of cardiomyocytes with arrhythmogenic potential. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.