Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKIIδ signaling pathways / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>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 II&delta; (CaMKII&delta;) 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.</p><p><b>METHODS</b>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 CaMKII&delta; was detected by RT-PCR.</p><p><b>RESULTS</b>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 CaMKII&delta; A and B were significantly upregulated and mRNA expression of CaMKII&delta; 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 CaMKII&delta; (all P < 0.05).</p><p><b>CONCLUSION</b>Metoprolol attenuates pressure overload-induced cardiac hypertrophy possibly through modulating Dryk1A-ASF-CaMKII&delta; signaling pathways.</p>