The role of CaMKII in diabetic heart dysfunction
The role of CaMKII in diabetic heart dysfunction
复制标题
DOI：
10.1007/s10741-015-9498-3
复制
发表时间：
2015-09-01
影响因子：
4.6
通讯作者：
Erickson, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Daniels, Lorna;Bell, James R.;Erickson, Jeffrey R.
糖尿病（DM）是一种日益严重的流行病，给世界各地的卫生服务造成了重大负担。糖尿病患者的心力衰竭（HF）发生率明显高于非糖尿病患者。DM和HF之间联系的一个潜在机制是钙调素依赖性蛋白激酶（CaMKII delta）的激活。在心肌兴奋-收缩和兴奋-转录耦合过程中，CaMKII δ介导离子通道功能和Ca2+处理。CaMKII δ活性在糖尿病患者和糖尿病小鼠模型的心肌中上调，促进包括肥大、纤维化和凋亡在内的病理信号传导。CaMKII delta的药理学抑制和敲除模型显示出CaMKII delta抑制具有潜在的治疗益处，有报道称CaMKII delta抑制可防止心脏肥大和细胞凋亡。本文将重点介绍CaMKII delta在糖尿病中的病理作用，并讨论CaMKII delta作为糖尿病的治疗靶点，以及运动对CaMKII delta的影响。
Diabetes mellitus (DM) is an increasing epidemic that places a significant burden on health services worldwide. The incidence of heart failure (HF) is significantly higher in diabetic patients compared to non-diabetic patients. One underlying mechanism proposed for the link between DM and HF is activation of calmodulin-dependent protein kinase (CaMKII delta). CaMKII delta mediates ion channel function and Ca2+ handling during excitation-contraction and excitation-transcription coupling in the myocardium. CaMKII delta activity is up-regulated in the myocardium of diabetic patients and mouse models of diabetes, where it promotes pathological signaling that includes hypertrophy, fibrosis and apoptosis. Pharmacological inhibition and knockout models of CaMKII delta have shown some promise of a potential therapeutic benefit of CaMKII delta inhibition, with protection against cardiac hypertrophy and apoptosis reported. This review will highlight the pathological role of CaMKII delta in diabetes and discuss CaMKII delta as a therapeutic target in DM, and also the effects of exercise on CaMKII delta.