Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice.

Background: Our previous study showed that diacylglycerol kinase ζ (DGKζ), which degenerates diacylglycerol (DAG), inhibits ventricular structural remodeling and rescues activated G protein αq (Gαq)–induced heart failure. However, whether DGKζ inhibits atrial remodeling is still unknown. Objective: This study aimed to elucidate the effects of DGKζ on atrial remodeling. Methods: A transgenic mouse (Gαq-TG) with cardiac expression of activated Gαq and a double transgenic mouse (Gαq/DGKζ-TG) with cardiac overexpression of DGKζ and activated Gαq were created. Results: During electrocardiogram (ECG) recording for 10 min, atrial fibrillation was observed in 5 of 11 anesthetized Gαq-TG mice but not in any wild-type (WT) and Gαq/DGKζ-TG mice (P <.05). All of the ECG parameters measured were prolonged in the Gαq-TG compared with WT mice. Interestingly, in Gαq/DGKζ-TG mice, although the PR and RR intervals were still prolonged, the P interval, QRS complex, and QT interval were not different from those in WT mice. In Langendorff-perfused hearts, the incidence of atrial tachyarrhythmia induced by rapid atrial pacing was greater in Gαq-TG hearts than in Gαq/DGKζ-TG hearts (P <.05). Action potential duration prolongation and impulse conduction slowing were observed in Gαq-TG atria compared with Gαq/DGKζ-TG atria. Dilatation of the left atrium with thrombus formation was observed in 9 Gαq-TG hearts but not in any Gαq/DGKζ-TG hearts. Moreover, the degree of extensive interstitial fibrosis in the left atrium was greater in Gαq-TG hearts than that in Gαq/DGKζ-TG hearts (P <.05). Conclusion: These results show that DGKζ inhibits Gαq-induced atrial remodeling and suggest that DGKζ is a novel therapeutic target for atrial fibrillation. [Copyright &y& Elsevier]