Belke Darrell D, Dillmann Wolfgang H
Department of Medicine, University of California, San Diego, 5063 Basic Sciences Building, La Jolla, CA 92093-0618, USA.
Curr Hypertens Rep. 2004 Dec;6(6):424-9. doi: 10.1007/s11906-004-0035-3.
Diabetes results in a cardiomyopathy characterized by reduced contractility that is primarily the result of changes in calcium handling within the myocyte. Because most of the calcium involved in excitation-contraction (EC) coupling is derived from the sarcoplasmic reticulum (SR), it is no surprise that many studies have found a reduction in sarco-endoplasmic reticulum calcium ATPase (SERCA) activity in the diabetic state. In this review, we outline the changes to SR calcium handling in the diabetic state and, through the use of transgenic mice and adenoviral gene therapy, we examine how SR function can be improved by the expression of various proteins that are directly and indirectly involved in calcium handling. Improving SERCA activity plays an important role in ameliorating the contractile phenotype associated with the diabetic state.
糖尿病会导致一种以收缩力降低为特征的心肌病,这主要是心肌细胞内钙处理变化的结果。由于参与兴奋 - 收缩(EC)偶联的大部分钙来自肌浆网(SR),因此许多研究发现糖尿病状态下肌浆网钙ATP酶(SERCA)活性降低也就不足为奇了。在这篇综述中,我们概述了糖尿病状态下SR钙处理的变化,并通过使用转基因小鼠和腺病毒基因疗法,研究如何通过表达直接和间接参与钙处理的各种蛋白质来改善SR功能。提高SERCA活性在改善与糖尿病状态相关的收缩表型方面起着重要作用。