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Investigating the role of neutrophil extracellular traps in the failing heart

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 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 goal of this project to investigate how NETs contribute to this process. We will: 1) Delineate the kinetics of NET formation after cardiac injury; 2) Follow the downstream consequences of modulating NET formation and 3) Investigate NETs in patients at high risk of developing HF. 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.

Date:1 Oct 2020 →  Today
Keywords:neutrophil, heart failure, fibrosis
Project type:PhD project