Project: “Casting NETs in the fibrotic heart”

Acronym	FIBRONETx (Reference Number: JTC-2019_060)
Duration	01/05/2020 - 30/04/2023
Project Topic	Neutrophils can release their nuclear contents lined with granule proteins, creating fibrous DNA nets with antimicrobial properties, called neutrophil extracellular traps (NETs). NETs also promote thrombus formation by providing a scaffold for platelet and clotting factor binding. The release of NETs thus shifts from a protective, immune defense mechanism, to a process with pathological consequences. The early NET inducer peptidylarginine deiminase 4 (PAD4) contributes to cardiac fibrosis development during aging in mice. PAD4-deficiency and NET degradation similarly protected from aberrant collagen deposition and decline in cardiac output after injury. In humans, this type of decline in function is linked to progression to heart failure (HF) with poor prognosis, often due to an increase in cardiac fibrotic remodeling with an unknown cause. HF occurs when the heart cannot properly pump blood to the rest of the body. When heart muscle is damaged and tries to repair itself, widespread scar tissue (fibrosis) is left behind. The main goal of the FIBRONETx consortium is to investigate how NETs contribute to this process. We will: 1) Follow the downstream consequences of modulating NET formation, 2) Link NETs to functional imaging in congenital heart disease patients at high risk of developing HF, 3) Investigate the impact of gender and pregnancy on NETs and cardiac fibrosis, and 4) Correlate NETs with thrombosis markers in blood collected from within the fibrotic hearts of patients who are prone to developing strokes. With this project we aim to better elucidate HF pathogenesis and to provide insight into future diagnostic use of NETs in the context of HF and thrombosis.
Network	ERA-CVD
Call	ERA-CVD Joint Transnational Call 2019

Project partner

Number	Name	Role	Country
1	KU Leuven	Coordinator	Belgium
2	Hôpital Européen Georges Pompidou	Partner	France
3	Universitäts-Herzzentrum Freiburg	Partner	Germany