title: Diacylglycerol kinase zeta inhibits G(alpha)q-induced atrial remodeling in transgenic mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  This study aimed to elucidate the effects of DGKzeta on atrial remodeling.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These results show that DGKzeta inhibits G(alpha)q-induced atrial remodeling and suggest that DGKzeta is a novel therapeutic target for atrial fibrillation.
authors.affiliation: Department of Molecular Pharmacology, Shinshu University School of Medicine, Nagano, Japan. address: mhirose@shinshu-u.ac.jp
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hirose
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niizeki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shimojo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakada
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mende
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019852:Diacylglycerol Kinase / Q000494:pharmacology*; D018450:Disease Progression; D004562:Electrocardiography; D005355:Fibrosis; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000096:biosynthesis*; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019852:Diacylglycerol Kinase; D043802:GTP-Binding Protein alpha Subunits, Gq-G11