CaMKⅡ在心血管疾病中作用的研究进展

Research progress on the role of Ca MKⅡin cardiovascular disease

钙离子/钙调素依赖性蛋白激酶Ⅱ(Ca MKⅡ)具有多重作用,并在心血管事件中有着举足轻重的地位。特别是其可以作用于多种分子信号通路中的下游靶点,导致血管疾病、心力衰竭、心肌肥厚和心律失常发生发展。Ca MKⅡ通过磷酸化L型钙通道、兰尼碱受体(Ry R2)和受磷蛋白(PLN)等多种钙调蛋白能够影响心肌细胞钙平衡、增加钙渗漏,亦可影响钠通道及钾通道,调节晚钠电流及ATP敏感性钾电流IKATP。此外更可直接通过激活丝裂原活化蛋白激酶(MAPKs)及脱乙酰化酶(HDAC)影响心肌细胞转录调控。这些机制在心肌肥厚、心力衰竭、心律失常的发生发展中都有着重要作用。因此深入了解Ca MKⅡ的结构与作用机制将有助于制定新的心血管疾病治疗策略。

Calcium/calmodulin-dependent protein kinaseⅡ（Ca MKⅡ） has multiple functions, which made it play acentral role in cardiovascular disease. Especially it activates numerous downstream targets in various signaling pathways thatpromotes vascular disease, heart failure, myocardial hypertrophy and arrhythmias. Ca MKⅡ can impact calcium balance andincrease calcium leak in myocardial cell via phosphorylating L type calcium channel, Ryanodine receptor（Ry R2） and phos-pholamban（PLN）, and regulate ATP sensitive potassium current（IKATP） and late sodium current by affecting sodium channelsand potassium channels. In addition, It can directly regulate transcription via activating the silk crack the original activatedprotein kinases（MAPKs） and acetylation enzyme（HDAC）. These mechanisms have important roles in myocardial hypertro-phy, heart failure and arrhythmia. So we focus to demonstrating the structure and action mechanism of Ca MKⅡ to improve anew therapy of cardiovascular disease.