کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2924056 | 1175893 | 2009 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice](/preview/png/2924056.png)
BackgroundOur 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.ObjectiveThis study aimed to elucidate the effects of DGKζ on atrial remodeling.MethodsA 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.ResultsDuring 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).ConclusionThese results show that DGKζ inhibits Gαq-induced atrial remodeling and suggest that DGKζ is a novel therapeutic target for atrial fibrillation.
Journal: Heart Rhythm - Volume 6, Issue 1, January 2009, Pages 78–84