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首页> 外文期刊>Circulation journal >Increased Phosphorylation of Ca2+ Handling Proteins as a Proarrhythmic Mechanism in Myocarditis
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Increased Phosphorylation of Ca2+ Handling Proteins as a Proarrhythmic Mechanism in Myocarditis

机译:Ca 2 + 处理蛋白磷酸化水平升高是心肌炎的心律失常机制

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Background: Because fatal arrhythmia is an important cause of death in patients with myocarditis, we investigated the proarrhythmic mechanisms of experimental autoimmune myocarditis. Methods?and?Results: Myocarditis was induced by injection of 2 mg porcine cardiac myosin into the footpads of adult Lewis rats on days 1 and 8 (Myo, n=15) and the results compared with Control rats (Control, n=15). In an additional 15 rats, 6 mg/kg prednisolone was injected into the gluteus muscle before the injection of porcine cardiac myosin on days 1 and 8 (MyoS, n=15). Hearts with myocarditis had longer action potential duration (APD), slower conduction velocity (CV; P2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor (KN93) treated Myo rats (n=0/5, P=0.01). CaMKII autophosphorylation at Thr287 (201%), and RyR2 phosphorylation at Ser2808 (protein kinase A/CaMKII site, 126%) and Ser2814 (CaMKII site, 21%) were increased in rats with myocarditis and reversed by steroid. Conclusions: The myocarditis group had an increased incidence of arrhythmia caused by increased phosphorylation of Ca2+handling proteins. These changes were partially reversed by an antiinflammatory treatment and CaMKII inhibition. ( Circ J 2014; 78: 2292–2301)
机译:背景:由于致命性心律失常是心肌炎患者死亡的重要原因,因此我们研究了实验性自身免疫性心肌炎的心律失常机制。方法和结果:在第1天和第8天(Myo,n = 15)向成年Lewis大鼠的脚垫注射2 mg猪心肌肌球蛋白诱导心肌炎,结果与对照组(对照组,n = 15)比较。在另外的15只大鼠中,在第1天和第8天注射猪心脏肌球蛋白之前,将6 mg / kg泼尼松龙注射到臀肌中(MyoS,n = 15)。心肌炎患者的动作电位持续时间(APD)较长,传导速度(CV; P2 + /钙调蛋白依赖性蛋白激酶II(CaMKII)抑制剂(KN93))治疗的Myo大鼠(n = 0/5,P = 0.01 )。在心肌炎大鼠中,Thr287处的CaMKII自磷酸化(201%)和Ser2808(蛋白激酶A / CaMKII位点,126%)和Ser2814(CaMKII位点,21%)的RyR2磷酸化增加,并被类固醇逆转。心肌炎组因Ca 2 + 处理蛋白的磷酸化增加导致心律失常的发生率增加,这些变化在一定程度上被抗炎药和CaMKII抑制所逆转(Circ J 2014; 78:2292-2301)。

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