Kids Heart Research and Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, Australia.
Int J Exp Pathol. 2011 Feb;92(1):57-65. doi: 10.1111/j.1365-2613.2010.00750.x. Epub 2010 Dec 1.
Cardiomyopathy contributes to morbidity and mortality in Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disorder. A major feature of the hearts of DMD patients and the mdx mouse model of the disease is cardiac fibrosis. Connective tissue growth factor (CTGF) is involved in the fibrotic process in many organs. This study utilized the mdx mouse model to assess the role of CTGF and other extracellular matrix components during the development of fibrosis in the dystrophic heart. Left ventricular function of mdx and control mice at 6, 29 and 43 weeks was measured by echocardiography. Young (6 weeks old) mdx hearts had normal function and histology. At 29 weeks of age, mdx mice developed cardiac fibrosis and increased collagen expression. The onset of fibrosis was associated with increased CTGF transcript and protein expression. Increased intensity of CTGF immunostaining was localized to fibrotic areas in mdx hearts. The upregulation of CTGF was also concurrent with increased expression of tissue inhibitor of matrix metalloproteinases (TIMP-1). These changes persisted in 43 week old mdx hearts and were combined with impaired cardiac function and increased gene expression of transforming growth factor (TGF)-β1 and matrix metalloproteinases (MMP-2, MMP-9). In summary, an association was observed between cardiac fibrosis and increased CTGF expression in the mdx mouse heart. CTGF may be a key mediator of early and persistent fibrosis in dystrophic cardiomyopathy.
心肌病导致杜兴氏肌营养不良症（DMD）患者的发病率和死亡率升高，这是一种进行性肌肉消耗性疾病。DMD 患者和疾病的 mdx 小鼠模型的心脏的一个主要特征是心脏纤维化。结缔组织生长因子（CTGF）参与许多器官的纤维化过程。本研究利用 mdx 小鼠模型来评估 CTGF 及其他细胞外基质成分在疾病心脏纤维化发展过程中的作用。通过超声心动图测量 mdx 小鼠和对照小鼠在 6、29 和 43 周时的左心室功能。年轻（6 周龄）mdx 心脏的功能和组织学正常。在 29 周龄时，mdx 小鼠发生了心脏纤维化和胶原表达增加。纤维化的发生与 CTGF 转录本和蛋白表达的增加有关。在 mdx 心脏中，CTGF 免疫染色强度增加的部位定位于纤维化区域。CTGF 的上调也与基质金属蛋白酶抑制剂（TIMP-1）的表达增加同时发生。这些变化在 43 周龄的 mdx 心脏中持续存在，并伴有心脏功能受损和转化生长因子（TGF）-β1 和基质金属蛋白酶（MMP）-2、MMP-9 的基因表达增加。总之，在 mdx 小鼠心脏中观察到心脏纤维化与 CTGF 表达增加之间存在关联。CTGF 可能是营养不良性心肌病中早期和持续纤维化的关键介质。
