title: Diacylglycerol kinase zeta attenuates pressure overload-induced cardiac hypertrophy.
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.
  
  
  RESULTS
  Thoracic transverse aortic constriction (TAC) was created in transgenic mice with cardiac-specific overexpression of DGKzeta (DGKzeta-TG) and wild-type (WT) mice. Increases in heart weight at 4 weeks after TAC were attenuated in DGKzeta-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 DGKzeta-TG mice. In WT mice, cardiac fibrosis and up-regulation of profibrotic genes, such as transforming growth factor-beta1, 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-beta1, were blocked in DGKzeta-TG mice.
  
  
  CONCLUSIONS
  These results are the first in vivo evidence that DGKzeta suppresses cardiac hypertrophy and fibrosis and prevents impaired left ventricular systolic function caused by pressure overload.
authors.affiliation: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Harada
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.forename: Takanori
authors.initials: T
authors.lastname: Arimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niizeki
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kitahara
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
authors.forename: Richard A
authors.initials: RA
authors.lastname: Walsh
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D003251:Constriction, Pathologic / Q000503:physiopathology; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004452:Echocardiography; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D019852:Diacylglycerol Kinase; C512480:diacylglycerol kinase zeta, mouse