Document Detail


Diacylglycerol kinase zeta inhibits G(alpha)q-induced atrial remodeling in transgenic mice.
MedLine Citation:
PMID:  19121805     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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). CONCLUSION: 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:
Masamichi Hirose; Yasuchika Takeishi; Takeshi Niizeki; Hisashi Shimojo; Tsutomu Nakada; Isao Kubota; Jun Nakayama; Ulrike Mende; Mitsuhiko Yamada
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2008-10-15
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  6     ISSN:  1556-3871     ISO Abbreviation:  Heart Rhythm     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-04-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  78-84     Citation Subset:  IM    
Affiliation:
Department of Molecular Pharmacology, Shinshu University School of Medicine, Nagano, Japan. address: mhirose@shinshu-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Atrial Fibrillation / drug therapy*,  metabolism,  physiopathology
Diacylglycerol Kinase / pharmacology*
Disease Progression
Electrocardiography
Fibrosis
GTP-Binding Protein alpha Subunits, Gq-G11 / biosynthesis*
Heart Atria / metabolism*,  pathology,  physiopathology
Heart Rate
Mice
Mice, Transgenic
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
EC 2.7.1.107/Diacylglycerol Kinase; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gq-G11
Comments/Corrections
Comment In:
Heart Rhythm. 2009 Jan;6(1):85-6   [PMID:  19121806 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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