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首页> 外文期刊>Circulation research: a journal of the American Heart Association >Dystroglycan matrix receptor function in cardiac myocytes is important for limiting activity-induced myocardial damage.
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Dystroglycan matrix receptor function in cardiac myocytes is important for limiting activity-induced myocardial damage.

机译：心肌细胞中的dystroglycan基质受体功能对于限制活性引起的心肌损伤很重要。

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RATIONALE: Genetic mutations in a number of putative glycosyltransferases lead to the loss of glycosylation of dystroglycan and loss of its laminin-binding activity in genetic forms of human muscular dystrophy. Human patients and glycosylation defective myd mice develop cardiomyopathy with loss of dystroglycan matrix receptor function in both striated and smooth muscle. OBJECTIVE: To determine the functional role of dystroglycan in cardiac muscle and smooth muscle in the development of cardiomyopathy in muscular dystrophies. METHODS AND RESULTS: Using cre/lox-mediated gene targeting, we show here that loss of dystroglycan function in ventricular cardiac myocytes is sufficient to induce a progressive cardiomyopathy in mice characterized by focal cardiac fibrosis, increase in cardiac mass, and dilatation ultimately leading to heart failure. In contrast, disruption of dystroglycan in smooth muscle is not sufficient to induce cardiomyopathy. The specific loss of dystroglycan function in cardiac myocytes causes the accumulation of large, clustered patches of myocytes with membrane damage, which increase in number in response to exercise-induced cardiac stress, whereas exercised mice with normal dystroglycan expression accumulate membrane damage limited to individual myocytes. CONCLUSIONS: Our findings suggest dystroglycan function as an extracellular matrix receptor in cardiac myocytes plays a primary role in limiting myocardial damage from spreading to neighboring cardiac myocytes, and loss of dystroglycan matrix receptor function in cardiac muscle cells is likely important in the development of cardiomyopathy in glycosylation-deficient muscular dystrophies.
机译：理由：许多假定的糖基转移酶中的遗传突变导致肌营养不良的糖基化功能障碍的糖基化损失和其层粘连蛋白结合活性的损失。人类患者和糖基化缺陷型myd小鼠会出现心肌病，横纹肌和平滑肌中的dystroglycan基质受体功能丧失。目的：确定肌营养不良蛋白在心肌和平滑肌中在肌营养不良性心肌病发展中的功能。方法和结果：使用cre / lox介导的基因靶向，我们在这里表明，心室心肌细胞中dystroglycan功能的丧失足以诱发以局灶性心脏纤维化，心脏质量增加和扩张为最终特征的小鼠进行性心肌病心脏衰竭。相反，破坏平滑肌中的dystroglycan不足以诱发心肌病。心肌细胞中特定的dystroglycan功能丧失会导致大量的成簇簇的心肌细胞积聚，并伴有膜损伤，响应运动引起的心脏压力，其数量会增加，而运动dystroglycan表达正常的小鼠累积的膜损伤仅限于单个心肌细胞。结论：我们的研究结果表明，dystroglycan在心肌细胞中作为细胞外基质受体发挥了主要作用，在限制心肌扩散至邻近的心肌细胞时发挥了主要作用，并且心肌细胞中dystroglycan基质受体功能的丧失可能在心肌病发展中起重要作用。糖基化缺陷型肌营养不良症。

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