钙/钙调蛋白依赖性蛋白激酶Ⅱ及其抑制剂在心力衰竭中的研究进展

Research Progress of Calcium/Calmodulin-dependent Protein KinaseⅡand Its Inhibitors in Heart Failure

心力衰竭(HF)是多种心脏疾病的终末共同通道,患者病死率高,生存质量差,已成为重要的公共卫生问题之一。在HF发展过程发生的大量分子变化中,蛋白激酶途径的改变通常起关键的介导作用,蛋白激酶将上游病理应激信号与下游调节程序联系在一起,从而影响心肌结构和功能的完整性。钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)是一种重要的蛋白激酶,它控制着各种各样的钙离子依赖性过程。在心肌细胞中,CaMKⅡ直接调节许多离子通道和钙转运调控蛋白,并控制越来越多的转录本及其下游产物的表达。CaMKⅡ是心脏应激时电生理和收缩反应的中心介质,在心脏疾病中的过度激活与HF和心律失常有关。

Heart failure(HF)is the common end-channel of many heart diseases,with high mortality and poor quality of life,and has become one of the important public health problems.Among the numerous molecular changes that occur during the development of HF,changes in protein kinase pathways often play a key mediating role.Protein kinases can associate the upstream pathologic stress signaling with downstream regulatory programs to affect both the structural and functional integrity of the heart muscle.Calcium/calmodulin-dependent protein kinaseⅡ(CaMKII)is an important protein kinase which controls various calciumion-dependent processes.In cardiomyocytes,CaMKII directly regulates numerous ion channels and calcium transport regulatory proteins and controls the expression of the transcripts with an ever-increasing number and their downstream products.CaMKII is the central mediator of electrophysiological and contractile responses during cardiac stress,and its hyper-activation in cardiac diseases is associated with HF and arrhythmias.