Clusterin protects against HFpEF by inhibiting UCHL1-mediated NLRP3 deubiquitylation and inflammasome activation.

ABSTRACT:

Background

Heart failure with preserved ejection fraction (HFpEF) poses a serious threat to human health, but effective treatment strategies remain limited. Clusterin (CLU) is a multifunctional glycoprotein implicated in inflammation and tissue remodeling, but its role in HFpEF pathogenesis is not fully understood.

Methods

The effects of CLU in a murine HFpEF model were investigated by adeno-associated virus (AAV)-mediated overexpression and liver-specific knockout approaches. Cardiac function in mice was evaluated by echocardiography, and myocardial inflammation and fibrosis were assessed using Masson's trichrome staining, real-time qPCR, and Western blot analysis. Protein interactions were identified by immunoprecipitation-mass spectrometry (IP-MS).

Results

AAV-medi

SUBMITTER: Yu J 

PROVIDER: S-EPMC12835627 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature