Neutrophil extracellular traps and peptidylarginine deiminase 4–mediated inflammasome activation link diabetes to cardiorenal injury and heart failure
Authors' conclusion
Diabetes promotes neutrophil inflammasome activation and NETosis, driving cardiac and renal inflammation and fibrosis. Peptidylarginine deiminase 4 deficiency prevents heart failure and preserves kidney function in experimental diabetes.
Study context
- Population
- Heart failure (HF) patients with or without diabetes (endomyocardial biopsies); Wild-type (WT) and PAD4⁻/⁻ mice with streptozotocin (STZ)-induced diabetes
- Participants
- 20 HF patients' biopsies
- Comparison
- PAD4⁻/⁻ vs WT mice with STZ-induced diabetes
Methodological detailshuman endomyocardial biopsies, STZ-induced diabetic mouse model
- Human endomyocardial biopsies
- STZ-induced diabetic mouse model
Main finding
As reported in the abstract
- Myocardial NET burden increased in HF patients with diabetes
- High glucose triggered inflammasome activation in human neutrophils
- Both PAD4⁻/⁻ and WT mice developed hyperglycaemia and weight loss after STZ; only WT neutrophils showed increased NETosis and ASC speck formation
- Only diabetic WT mice had elevated IL-1β and von Willebrand factor (VWF), impaired cardiac function, reduced exercise tolerance and pulmonary oedema; PAD4⁻/⁻ mice protected
- WT diabetic hearts and kidneys: greater fibrosis, neutrophil infiltration, neutrophil extracellular traps (NETs) and TGF-β1
- WT mice: albuminuria and renal fibrosis; PAD4⁻/⁻ mice preserved renal function
Original publication
Neutrophil extracellular traps and peptidylarginine deiminase 4–mediated inflammasome activation link diabetes to cardiorenal injury and heart failure. Eur Heart J. Published 27 November 2025. doi:10.
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