Diacylglycerol Kinase .XI. Attenuates Pressure Overload-Induced Cardiac Hypertrophy

Accession number;07A0135132
Title;Diacylglycerol Kinase .XI. Attenuates Pressure Overload-Induced Cardiac Hypertrophy
Author;HARADA MUTSUO(Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine)   TAKEISHI YASUCHIKA(Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine)   ARIMOTO TAKANORI(Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine)   NIIZEKI TAKESHI(Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine)   KITAHARA TATSURO(Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine)   GOTO KAORU(Department of Anatomy and Cell Biology, Yamagata University School of Medicine)   WALSH RICHARD A.(Department of Medicine, Case Western Reserve University)   KUBOTA ISAO(Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine)   
Journal Title;Circ J
Journal Code:F0908A
ISSN:1346-9843
VOL.71;NO.2;PAGE.276-282 (J-STAGE)(2007)
Figure&Table&Reference;FIG.7, REF.37
Pub. Country;Japan
Language;English
Abstract;Background The Gaq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in the development of cardiac hypertrophy and heart failure. DAG kinase (DGK) phosphorylates DAG and controls cellular DAG levels, thus acting as a regulator of GPCR signaling. It has been previously reported that DGK inhibited GPCR agonist-induced activation of the DAG-PKC signaling and subsequent cardiomyocyte hypertrophy, so the purpose of this study was to examine whether DGK modifies the development of cardiac hypertrophy induced by pressure overload. Methods and Results Thoracic transverse aortic constriction (TAC) was created in transgenic mice with cardiac-specific overexpression of DGK.XI. (DGK.XI.-TG) and wild-type (WT) mice. Increases in heart weight at 4 weeks after TAC were attenuated in DGK.XI.-TG mice compared with WT mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in WT mice were observed with echocardiography at 4 weeks after TAC surgery. However, these structural and functional changes after TAC were attenuated in DGK.XI.-TG mice. In WT mice, cardiac fibrosis and up-regulation of profibrotic genes, such as transforming growth factor-.BETA.1, collagen type I, and collagen type III, were observed at 4 weeks after TAC. However, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor-.BETA.1, were blocked in DGK.XI.-TG mice. Conclusion These results are the first in vivo evidence that DGK.XI. suppresses cardiac hypertrophy and fibrosis and prevents impaired left ventricular systolic function caused by pressure overload. (Circ J 2007; 71: 276 - 282) (Author abst.)