| 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 |
Related Documents
:
|
10912515 - The relative importance of endocrine versus autocrine/paracrine insulin-like growth fac... 14726475 - Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-a... 19913415 - Attenuation of adverse cardiac effects in prednisolone-treated delta-sarcoglycan-defici... 18519735 - Desmin mediates tnf-alpha-induced aggregate formation and intercalated disk reorganizat... 1951475 - Soluble immune complexes stimulate production of interleukin-1 by cultured rat glomerul... 23396115 - Maladaptive exploratory behavior and neuropathology of the ps-1 p117l alzheimer transge... |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hyperchol...
Next Document: Antiarrhythmic effect of IKr activation in a cellular model of LQT3.