Neutrophil extracellular traps and peptidylarginine deiminase 4-mediated inflammasome activation link diabetes to cardiorenal injury and heart failure.

ABSTRACT:

Background and aims

Diabetes is associated with increased risk of cardiovascular and renal disease. This study investigated the role of peptidylarginine deiminase 4 (PAD4), neutrophil extracellular traps (NETs), and inflammasome activation in diabetic cardiomyopathy (DCM) and kidney disease (DKD).

Methods

Endomyocardial biopsies (EMB) from heart failure (HF) patients (n = 20) with or without diabetes were stained for NETs. Wild-type (WT) and PAD4⁻/⁻ mice were subjected to streptozotocin (STZ)-induced diabetes and cardiac function, blood glucose, body weight, and exercise tolerance were assessed longitudinally. NETosis and ASC specks were evaluated in mouse and human neutrophils. Cardiac and renal fibrosis was assessed by Sirius Red/Fast Green staining. Confocal microscopy, E

SUBMITTER: Schommer N 

PROVIDER: S-EPMC12751317 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature