Experimental models of duchenne muscular dystrophy: relationship with cardiovascular disease.
Experimental models of duchenne muscular dystrophy: relationship with cardiovascular disease.
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DOI：
10.2174/1874192401004010265
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发表时间：
2010-11-26
期刊：
影响因子：
--
通讯作者：
Robson LG
中科院分区：
文献类型：
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作者：
Ameen V;Robson LG
几乎每个患有杜氏肌营养不良症（DMD）的男孩都会出现心脏问题。然而，呼吸问题曾经是这些DMD男孩死亡的主要原因;随着更好的呼吸护理的出现，现在心脏受累正成为他们死亡的最常见原因。一旦心脏受到影响，随着时间的推移，心脏功能会逐渐恶化。主要问题是心肌细胞的死亡。心肌细胞死亡的原因是由于肌营养不良蛋白的丢失，这使得肌膜更容易受到损伤，并导致钙内流、钙激活蛋白酶的级联反应，最终导致心肌细胞死亡。死亡的心肌细胞被纤维化组织取代，这导致扩张型心肌病（DCM）的发展，其开始于左心室的基部，并发展到涉及整个左心室。用于DMD心肌病的治疗是基于设计用于其他形式的心脏无力的治疗，包括ACE抑制剂和β受体阻滞剂。基于DMD病理生理学的新疗法正在推出。这篇综述将着眼于DMD心脏问题的病理生理学，以及如何利用现有的各种动物模型为DMD男孩设计新的治疗方案。
Almost every boy that has Duchenne Muscular Dystrophy (DMD) will develop cardiac problems. Whereas, it used to be respiratory problems that was the main cause of death in these DMD boys; with the advent of better respiratory care it is now the cardiac involvement that is becoming the most common cause of their death. Once the heart is affected, there is progressive deterioration in the function of the heart over time. The main problem is the death of the cardiomyocytes. The cause of the cardiomyocyte death is due to the loss of dystrophin, this makes the sarcolemma more susceptible to damage, and leads to a cascade of calcium influx, calcium activated proteases and ultimately the death of the cardiomyocyte. The dead cardiomyocytes are replaced by fibrotic tissue, which results in a dilated cardiomyopathy (DCM) developing, which begins in the base of the left ventricle and progresses to involve the entire left ventricle. The treatments used for the DMD cardiomyopathy are based on ones designed for other forms of cardiac weakness and include ACE-inhibitors and β-blockers. New therapies based around the pathophysiology in DMD are now being introduced. This review will look at the pathophysiology of the cardiac problems in DMD and how the various animal models that are available can be used to design new treatment options for DMD boys.