Polydatin Protects Against the Formation of PPE-Induced Abdominal Aortic Aneurysms in Mice by Activating Nuclear Factor Erythroid 2-Related Factor 2.

Abstract

Sudden death resulting from abdominal aortic aneurysm (AAA) rupture is a highly fatal cardiovascular condition. There remains an urgent need to identify innovative therapeutic strategies capable of decelerating AAA progression and rupture. Although polydatin (PLD) has been consistently shown to exert potent anti-inflammatory effects in diverse pathological contexts, its regulatory role in AAA has not yet been investigated. Using a porcine pancreatic elastase (PPE) infusion-induced AAA mouse model, we comprehensively evaluated PLD's influence on NRF2 signaling by Western blot (WB) analysis, immunohistochemistry (IHC), immunofluorescence (IF), flow cytometry (FC), and real-time quantitative PCR (RT-qPCR) tests. Our findings demonstrate that PLD robustly activates NRF2 pathway, thereby attenuating AAA formation by curbing smooth muscle cell (SMCs) phenotypic transformation and apoptosis, as well as suppressing macrophage-mediated inflammatory responses.