Diacylglycerol kinase zeta inhibits G(alpha)q-induced atrial remodeling in transgenic mice.

<bold>Background: </bold>Our previous study showed that diacylglycerol kinase zeta (DGKzeta), which degenerates diacylglycerol (DAG), inhibits ventricular structural remodeling and rescues activated G protein (alpha)q (G(alpha)q)-induced heart failure. However, whether DGKzeta inhibits atrial remodeling is still unknown.<bold>Objective: </bold>This study aimed to elucidate the effects of DGKzeta on atrial remodeling.<bold>Methods: </bold>A transgenic mouse (G(alpha)q-TG) with cardiac expression of activated G(alpha)q and a double transgenic mouse (G(alpha)q/DGKzeta-TG) with cardiac overexpression of DGKzeta and activated G(alpha)q were created.<bold>Results: </bold>During electrocardiogram (ECG) recording for 10 min, atrial fibrillation was observed in 5 of 11 anesthetized G(alpha)q-TG mice but not in any wild-type (WT) and G(alpha)q/DGKzeta-TG mice (P <.05). All of the ECG parameters measured were prolonged in the G(alpha)q-TG compared with WT mice. Interestingly, in G(alpha)q/DGKzeta-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 G(alpha)q-TG hearts than in G(alpha)q/DGKzeta-TG hearts (P <.05). Action potential duration prolongation and impulse conduction slowing were observed in G(alpha)q-TG atria compared with G(alpha)q/DGKzeta-TG atria. Dilatation of the left atrium with thrombus formation was observed in 9 G(alpha)q-TG hearts but not in any G(alpha)q/DGKzeta-TG hearts. Moreover, the degree of extensive interstitial fibrosis in the left atrium was greater in G(alpha)q-TG hearts than that in G(alpha)q/DGKzeta-TG hearts (P <.05).<bold>Conclusion: </bold>These results show that DGKzeta inhibits G(alpha)q-induced atrial remodeling and suggest that DGKzeta is a novel therapeutic target for atrial fibrillation. [ABSTRACT FROM AUTHOR]