Background: The prevalence of atrial fibrillation (AF), particularly associated with obesity, is on the rise worldwide. Ca²⁺/calmodulin-dependent protein kinase (CaMKII) is activated in the advanced condition of atrial remodeling. However, it is unclear whether CaMKII is activated and affects vulnerability to AF in the early phase of obesity. In this study, we examined the involvement of CaMKII in the inducibility and duration of AF in the early stage of diet-induced obese mice.
Methods: Mice were fed a normal chow diet (NCD) or high-fat diet (HFD). Following diet-loading for 2 weeks, HFD-fed mice were administrated CaMKII inhibitor. Induction of AF was performed by transesophageal atrial burst pacing. Furthermore, we evaluated the expression of CaMKII, blood pressure, and atrial fibrosis.
Results: HFD-fed mice increased the inducibility of AF compared to NCD mice. In addition, treatment with the CaMKII inhibitor in HFD-fed mice reduced the inducibility of AF. Expression of phosphorylated CaMKII is increased in HFD-fed mice. Inhibition of CaMKII didn‘t have effects on blood pressure, and fibrosis.
Conclusion: Inhibition of CaMKII reduced the inducibility of AF in the early phase of obesity without affecting atrial structural remodeling, suggesting that CaMKII is a factor that contributes to AF from the early stage of obesity.