Heart failure & cardiomyopathies
Von Willebrand factor exacerbates heart failure through formation of neutrophil extracellular traps
Authors' conclusion
This study established the role of a novel VWF-SLC44A2-NET axis in regulating mitochondrial homeostasis and function, leading to cardiac apoptosis and contributing to HF pathogenesis.
Study context
- Population
- Patients with heart failure (HF) and transverse aortic constriction (TAC) mouse models of HF
Methodological detailsPAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) used to evaluate neutrophil extracellular traps (NETs) in HF; RNA sequencing for downstream mechanisms; rhADAMTS13, ADAMTS13 and SLC44A2 knockouts to identify upstream factors
- PAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) used to evaluate NETs in HF; RNA sequencing for downstream mechanisms; rhADAMTS13, ADAMTS13 and SLC44A2 knockouts to identify upstream factors
Main finding
As reported in the abstract
- Elevated NET levels in patients with HF and TAC mouse models of HF
- PAD4 knockout and NET inhibitors improved cardiac function
- NETs induced mitochondrial dysfunction in cardiomyocytes, inhibiting mitochondrial biogenesis via NE-TLR4-mediated suppression of PGC-1α
- VWF/ADAMTS13 regulated NET formation via SLC44A2
- Sacubitril/valsartan amplifies cardioprotective effects of VWF-SLC44A2-NET axis blockade
Original publication
Von Willebrand factor exacerbates heart failure through formation of neutrophil extracellular traps. Eur Heart J. Published 21 August 2024. doi:10.
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