Berberine Inhibits Abdominal Aortic Aneurysm Formation and Vascular Smooth Muscle Cell Phenotypic Switching by Regulating the Nrf2 Pathway

Abdominal aortic aneurysm (AAA) is a life-threatening disease featuring extensive membrane destruction in the vascular wall, which is closely associated with the phenotypic switching of vascular smooth muscle cells (VSMC). A thorough understanding of the changes in regulatory factors during the pathogenesis of VSMC phenotypic switching is essential for medical treatments in AAA. NRF2 was deemed to hold a pivotal position in developing AAA, especially as it can regulate VSMC phenotypic switching. In this study, we found that berberine prevents the formation of AAA by regulating the phenotypic switching of VSMC, which was well validated in both in vitro and in vivo functional experiments. Mechanically, we found that berberine regulates VSMC phenotypic switching by promoting the expression of downstream VSMC contraction genes through the deubiquitination of Keap1, in which the deubiquitinating enzyme USP15 plays an important mediating role in this process.