Department of Medicine, Section of Cardiology, Center for Cardiovascular Research, University of Illinois at Chicago , IL 60612, USA.
J Mol Cell Cardiol. 2010 May;48(5):834-42. doi: 10.1016/j.yjmcc.2010.01.003. Epub 2010 Jan 15.
Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that frequently show inappropriate ventricular hypertrophy or dilation. Current data suggest that numerous mutations in several genes can cause cardiomyopathies, and the severity of their phenotypes is also influenced by modifier genes. Two major types of inherited cardiomyopathies include familial hypertrophic cardiomyopathy (FHC) and dilated cardiomyopathy (DCM). FHC typically involves increased myofilament Ca(2+) sensitivity associated with diastolic dysfunction, whereas DCM often results in decreased myofilament Ca(2+) sensitivity and systolic dysfunction. Besides alterations in myofilament Ca(2+) sensitivity, alterations in the levels of Ca(2+)-handling proteins have also been described in both diseases. Recent work in animal models has attempted to rescue FHC and DCM via modifications at the myofilament level, altering Ca(2+) homeostasis by targeting Ca(2+)-handling proteins, such as the sarcoplasmic reticulum ATPase and phospholamban, or by interfering with the products of different modifiers genes. Although attempts to rescue cardiomyopathies in animal models have shown great promise, further studies are needed to validate these strategies in order to provide more effective and specific treatments.
心肌病是一组与机械和/或电功能障碍相关的心肌疾病，常伴有心室肥厚或扩张。目前的数据表明，许多基因的突变都可能导致心肌病，其表型的严重程度也受到修饰基因的影响。两种主要类型的遗传性心肌病包括家族性肥厚型心肌病（FHC）和扩张型心肌病（DCM）。FHC 通常涉及肌丝 Ca(2+)敏感性增加，与舒张功能障碍有关，而 DCM 通常导致肌丝 Ca(2+)敏感性降低和收缩功能障碍。除了肌丝 Ca(2+)敏感性的改变外，两种疾病的 Ca(2+)处理蛋白水平也发生了改变。最近在动物模型中的研究试图通过肌丝水平的修饰来挽救 FHC 和 DCM，通过靶向 Ca(2+)处理蛋白（如肌浆网 ATP 酶和磷酸化肌球蛋白轻链）来改变 Ca(2+)稳态，或通过干扰不同修饰基因的产物来实现。尽管在动物模型中挽救心肌病的尝试显示出巨大的希望，但仍需要进一步的研究来验证这些策略，以提供更有效和更有针对性的治疗方法。
