Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKⅡδ signaling pathways
10.3760/cma.j.issn.0253-3758.2013.12.009
- VernacularTitle:美托洛尔对腹主动脉缩窄大鼠心肌双特异性酪氨酸磷酸化调节激酶1A-可变剪接因子-钙/钙调素依赖蛋白激酶Ⅱδ信号通路的影响
- Author:
Jian YAO
1
;
Hong-Zhuan SHENG
;
Xiao-Chen LU
;
Qing-Qing GU
;
Jian-Hua ZHU
Author Information
1. 南通大学医学院组胚教研室
- Keywords:
Myocardium;
Metoprolol
- From:
Chinese Journal of Cardiology
2013;41(12):1029-1033
- CountryChina
- Language:Chinese
-
Abstract:
Objective Previous study showed that the signaling pathway of dual-specificity tyrosinephosphorylated and regulated kinase 1 A (Dyrk1 A)-alternative splicing factor (ASF)-alternative splicing of Ca2+/calmodulin-dependent protein kinase Ⅱ δ (CaMK Ⅱ δ) 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 Dyrk1 A and ASF were determined by Western blot and mRNA expression of alternative splicing of CaMK Ⅱ δ was detected by RT-PCR.Results Four weeks after coarctation,cardiac hypertrophy was evidenced in rats of hypertensive group,and the protein expression of Dyrk1 A was significantly upregulated,while the expression of ASF was significantly downregulated,the mRNA expression of CaMK Ⅱ δ A and B were significantly upregulated and mRNA expression of CaMK Ⅱ δ 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 CaMK Ⅱ δ (all P ＜ 0.05).Conclusion Metoprolol attenuates pressure overloadinduced cardiac hypertrophy possibly through modulating Dryk1 A-ASF-CaMK Ⅱ δ signaling pathways.
