4.1 Major findings
The findings presented in this study demonstrate that isorhamnetin suppresses AngII-induced AF vulnerability through the inhibition of electrical and structural remodeling. Isorhamnetin alleviates abnormal diastolic intracellular Ca2+ activities by modulating CaMKII-mediated RyR2 and restores aberrant AP morphology via the regulation of Cav1.2 activation in reverse electrical remodeling. In addition, isorhamnetin prevents left atrial enlargement and severe fibrosis via the abrogation of TRPC-mediated MAPK and TGF-β pathways in reverse structural remodeling. To the best of our knowledge, this study is the first to investigate the potential mechanism by which natural flavonoids suppress vulnerability to AF.