title: [Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKIIδ signaling pathways].
abstract: OBJECTIVE
  Previous study showed that the signaling pathway of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A)-alternative splicing factor (ASF)- alternative splicing of Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is related to myocardial hypertrophy. The aim of present study was to determine the effect and related mechamism of metoprolol on pressure overload induced myocardial hypertrophy.
  
  
  METHODS
  Pressure overload-induced hypertension was induced by coarctation of suprarenal abdominal aorta in rats. Rats were randomly divided into sham-operated control, hypertension and hypertension plus metoprolol (30 mg×kg(-1)×d(-1)) groups (n = 10 each). Blood pressure, the left ventricular weight to body weight ratio and cardiomyocytes area were measured, the protein expression of Dyrk1A and ASF were determined by Western blot and mRNA expression of alternative splicing of CaMKIIδ was detected by RT-PCR.
  
  
  RESULTS
  Four weeks after coarctation, cardiac hypertrophy was evidenced in rats of hypertensive group, and the protein expression of Dyrk1A was significantly upregulated, while the expression of ASF was significantly downregulated, the mRNA expression of CaMKIIδ A and B were significantly upregulated and mRNA expression of CaMKIIδ C was significantly downregulated compared to those in sham-operated control rats (all P < 0.05). Treatment with metoprolol effectively attenuated cardiac hypertrophy and reversed pressure overload induced changes on Dyrk1A and ASF, and alternative splicing of CaMKIIδ (all P < 0.05).
  
  
  CONCLUSIONS
  Metoprolol attenuates pressure overload-induced cardiac hypertrophy possibly through modulating Dryk1A-ASF-CaMKIIδ signaling pathways.
authors: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Jian
authors: J
authors: Yao
authors: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Hong-zhuan
authors: HZ
authors: Sheng
authors: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Xiao-chen
authors: XC
authors: Lu
authors: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Qing-qing
authors: QQ
authors: Gu
authors: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China. Email:jianh_zhu@sina.com.
authors: Jian-hua
authors: JH
authors: Zhu
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction / Q000187:drug effects; D000097603:Dyrk Kinases
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008790:Metoprolol; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D000097603:Dyrk Kinases