Danuglipron Ameliorates Pressure Overload-Induced Cardiac Remodelling Through the AMPK Pathway.

ABSTRACT: Cardiac remodelling, a pathological process induced by various cardiovascular diseases, remains a significant challenge in clinical practice. Here, we investigate the potential of Danuglipron (PF-06882961, PF), a novel oral glucagon-like peptide-1 (GLP-1) receptor agonist, in alleviating pressure overload (PO)-induced cardiac hypertrophy and fibrosis. Using both in vivo and in vitro models, we demonstrate that PF treatment (1 mg/kg/day, orally for 8 weeks) significantly attenuates aortic banding-induced cardiac dysfunction and pathological remodelling in mice. Mechanistically, we show that PF mitigates apoptotic responses and enhances autophagy by promoting AMPK phosphorylation and increasing HSP70 expression. Notably, the cardioprotective effects of PF are abolished in AMPKα2 knockout mic

SUBMITTER: Wang P 

PROVIDER: S-EPMC11897056 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature