Potential of interferon-gamma and TNF-alpha to modulate electromechanical properties of human cardiomyocytes derived from induced pluripotent stem cells in vitro: implications to the pathophysiology of Chagas disease cardiomyopathy

• Grant number: 25/06422-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: May 31, 2029
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Edecio Cunha Neto
• Grantee: Mateus Braz Miceli
• 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: 22/00758-0 - Mitochondria, interferon-gamma and genetics in Chagas Disease cardiomyopathy: pathogenesis, therapeutic targets and prognostic markers, AP.TEM

Abstract

During chronic Chagas disease cardiomyopathy (CCC), inflammatory cytokines IFN-gamma and TNF-alpha have been implicated in the pathogenesis and progression of heart disease. Previous studies from literature have shown that both IFN-gamma and TNF-alpha are able to deteriorate in vitro electromechanical function of mouse cardiomyocytes Recently, our group has shown that both cytokines impair mitochondrial function of cardiomyocytes differentiated from inducible pluripotent stem cells (hCM-IPSC) obtained from Chagas disease patients carrying heterozygous loss-of-function variant on the mitochondrial enzyme DHODH R135C, involved in the electron transfer chain. However, the precise role of each cytokine or combination of both, in the electromechanical remodeling of human cardiomyocytes during CCC remains to be evaluated. Thus, in the present Ph.D project we aim to investigate whether and how IFN-gamma and TNF-alpha, or combination of both, impairs electromechanical properties of hCM-IPSC derived from CCC patients in vitro. (AU)