Effects of Sacubitril/Valsartan on the Expression of CaMKII/Ca v 1.2 in Atrial Fibrillation Stimulation Rabbit Model.

Methods: Overall, 18 rabbits were randomly divided into control, pacing (600 beats/min), and pacing+sac/val groups. The rabbits in the pacing+sac/val cohort received oral sac/val (10 mg/kg twice daily) across the 21-day investigation period. After three weeks, the atrial effective refractory period (AERP) and AF induction rate were compared. HL-1 cultures were exposed to fast pacing (24 h) with and without LBQ657 (active sacubitril form)/valsartan. Western blots were used for detecting Ca _v 1.2 and CaMKII expression within atrial muscles of the rabbits and HL-1 cultures of AF model.
Results: In comparison to the sham cohort, the AF induction rate was markedly increased together with AERP reduction within pacing cohort. Such changes were markedly rescued through sac/val treatment in pacing+sac/val cohort. The proteomic expression profiles of CaMKII and Ca _v 1.2 showed that the CaMKII expression was markedly upregulated, while Ca _v 1.2 expression was downregulated in the pacing cohort. Importantly, these effects were absent in pacing+sac/val cohort.
Conclusion: Results of this study show that sac/val treatment regulates the expression of CaMKII/Ca _v 1.2 and could alter this pathway in atrial rapid electrical stimulation models. Therefore, this investigation could contribute to a novel strategy in AF therapeutics in clinical settings.
Competing Interests: The authors declare that they have no conflicts of interest.
(Copyright © 2022 Qi Lou et al.)