| Full text | |
| Author(s): |
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.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 10, n. 1, p. 18-pg., 2020-09-30. |
| Abstract | |
Cardiac fibroblasts are present throughout the myocardium and are enriched in the microenvironment surrounding the ventricular conduction system (VCS). Several forms of arrhythmias are linked to VCS abnormalities, but it is still unclear whether VCS malformations are cardiomyocyte autonomous or could be linked to crosstalk between different cell types. We reasoned that fibroblasts influence cardiomyocyte specialization in VCS cells. We developed 2D and 3D culture models of neonatal rat cardiac cells to assess the influence of cardiac fibroblasts on cardiomyocytes. Cardiomyocytes adjacent to cardiac fibroblasts showed a two-fold increase in expression of VCS markers (NAV1.5 and CONTACTIN 2) and calcium transient duration, displaying a Purkinje-like profile. Fibroblast-conditioned media (fCM) was sufficient to activate VCS-related genes (Irx3, Scn5a, Connexin 40) and to induce action potential prolongation, a hallmark of Purkinge phenotype. fCM-mediated response seemed to be spatially-dependent as cardiomyocyte organoids treated with fCM had increased expression of connexin 40 and NAV1.5 primarily on its outer surface. Finally, NOTCH1 activation in both cardiomyocytes and fibroblasts was required for connexin 40 up-regulation (a proxy of VCS phenotype). Altogether, we provide evidence that cardiac fibroblasts influence cardiomyocyte specialization into VCS-like cells via NOTCH1 signaling in vitro. (AU) | |
| FAPESP's process: | 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases |
| Grantee: | Danilo Roman Campos |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/24577-8 - Nanostructures and iPSC derived cardiomyocytes approaches for cardiac protection and repair post-MI |
| Grantee: | Rafael Dariolli |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 18/22830-9 - Involvement of the Ca2+/ Calmodulin/CAMKII signaling axis in the electrical and contractile dysfunctions of the heart in the chronic phase of Chagas Disease |
| Grantee: | Artur Santos Miranda |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 15/50216-5 - Characterization of the optimal hiPSC-derived cardiac cell population for heart regeneration after myocardial infarction |
| Grantee: | José Eduardo Krieger |
| Support Opportunities: | Research Grants - Research Partnership for Technological Innovation - PITE |
| FAPESP's process: | 17/05829-4 - Evaluation of the influence of fibroblasts on maturation and induction of cardiomyocytes with arrhythmogenic potential |
| Grantee: | Agatha Ribeiro da Silva |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther |
| Grantee: | José Eduardo Krieger |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/09861-1 - The role of late sodium current in the inherited and acquired cardiac arrhythmias: from the biophysics properties to new therapeutic targets |
| Grantee: | Danilo Roman Campos |
| Support Opportunities: | Research Grants - Young Investigators Grants |