Holland Ashling, Ohlendieck Kay
Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland.
Biomed Res Int. 2014;2014:246195. doi: 10.1155/2014/246195. Epub 2014 Mar 20.
Cardiorespiratory complications are frequent symptoms of Duchenne muscular dystrophy, a neuromuscular disorder caused by primary abnormalities in the dystrophin gene. Loss of cardiac dystrophin initially leads to changes in dystrophin-associated glycoproteins and subsequently triggers secondarily sarcolemmal disintegration, fibre necrosis, fibrosis, fatty tissue replacement, and interstitial inflammation. This results in progressive cardiac disease, which is the cause of death in a considerable number of patients afflicted with X-linked muscular dystrophy. In order to better define the molecular pathogenesis of this type of cardiomyopathy, several studies have applied mass spectrometry-based proteomics to determine proteome-wide alterations in dystrophinopathy-associated cardiomyopathy. Proteomic studies included both gel-based and label-free mass spectrometric surveys of dystrophin-deficient heart muscle from the established mdx animal model of dystrophinopathy. Comparative cardiac proteomics revealed novel changes in proteins associated with mitochondrial energy metabolism, glycolysis, signaling, iron binding, antibody response, fibre contraction, basal lamina stabilisation, and cytoskeletal organisation. This review summarizes the importance of studying cardiomyopathy within the field of muscular dystrophy research, outlines key features of the mdx heart and its suitability as a model system for studying cardiac pathogenesis, and discusses the impact of recent proteomic findings for exploring molecular and cellular aspects of cardiac abnormalities in inherited muscular dystrophies.
心肺并发症是杜氏肌营养不良症的常见症状，这是一种由肌营养不良蛋白基因原发性异常引起的神经肌肉疾病。心肌肌营养不良蛋白的缺失最初会导致肌营养不良蛋白相关糖蛋白的变化，随后引发继发性肌膜解体、纤维坏死、纤维化、脂肪组织替代和间质炎症。这会导致进行性心脏病，这是相当一部分患有X连锁肌营养不良症患者的死因。为了更好地定义这种类型心肌病的分子发病机制，多项研究应用基于质谱的蛋白质组学来确定肌营养不良症相关心肌病中全蛋白质组的改变。蛋白质组学研究包括对来自已建立的肌营养不良症mdx动物模型的肌营养不良蛋白缺陷型心肌进行基于凝胶和无标记的质谱分析。比较心脏蛋白质组学揭示了与线粒体能量代谢、糖酵解、信号传导、铁结合、抗体反应、纤维收缩、基膜稳定和细胞骨架组织相关的蛋白质的新变化。本综述总结了在肌营养不良症研究领域中研究心肌病的重要性，概述了mdx心脏的关键特征及其作为研究心脏发病机制模型系统的适用性，并讨论了最近蛋白质组学研究结果对探索遗传性肌营养不良症中心脏异常的分子和细胞方面的影响。
