We describe the association of Becker muscular dystrophy (BMD) derived heart failure with the impairment of tissue homeostasis and remodeling capabilities of the affected heart tissue. We report that BMD heart failure is associated with a significantly decreased number of cardiovascular progenitor cells, reduced cardiac fibroblast migration, and ex vivo survival. Becker muscular dystrophy belongs to a class of genetically inherited dystrophin deficiencies. It affects male patients and results in progressive skeletal muscle degeneration and dilated cardiomyopathy leading to heart failure. It is a relatively mild form of dystrophin deficiency, which allows patients to be on a heart transplant list. In this unique situation, the explanted heart is a rare opportunity to study the degenerative process of dystrophin-deficient cardiac tissue. Heart tissue was excised, dissociated, and analyzed. The fractional content of c-kit+/CD45− cardiovascular progenitor cells (CVPCs) and cardiac fibroblast migration were compared to control samples of atrial tissue. Control tissue was obtained from the hearts of healthy organ donor’s during heart transplantation procedures. We report significantly decreased CVPCs (c-kit+/CD45−) throughout the heart tissue of a BMD patient, and reduced numbers of phase-bright cells presenting c-kit positivity in the dystrophin-deficient cultured explants. In addition, ex vivo CVPCs survival and cardiac fibroblasts migration were significantly reduced, suggesting reduced homeostatic support and irreversible tissue remodeling. Our findings associate genetically derived heart failure in a dystrophin-deficient patient with decreased c-kit+/CD45− CVPCs and their resilience, possibly hinting at a lack of cardioprotective capability and/or reduced homeostatic support. This also correlates with reduced plasticity of the explanted cardiac tissue, related to the process of irreversible remodeling in the BMD patient’s heart.

中文翻译：

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在受到贝克尔肌营养不良症影响的心肌中，心血管祖细胞和组织可塑性降低。

我们描述了贝克尔肌营养不良症（BMD）引起的心力衰竭与组织稳态和受影响心脏组织的重塑能力受损的关联。我们报告BMD心力衰竭与心血管祖细胞的数量显着减少，心脏成纤维细胞迁移减少和离体生存相关。贝克尔肌营养不良症属于一类遗传性肌营养不良蛋白缺乏症。它影响男性患者并导致进行性骨骼肌变性和扩张型心肌病，导致心力衰竭。肌营养不良蛋白缺乏症是一种相对温和的形式，可将患者列入心脏移植名单。在这种独特的情况下，离体心脏是研究肌营养不良蛋白缺乏的心脏组织退化过程的难得机会。切除心脏组织，解离并分析。将c-kit + / CD45-心血管祖细胞（CVPC）的分数含量和心脏成纤维细胞迁移与心房组织的对照样品进行了比较。在心脏移植过程中从健康器官供体的心脏获得对照组织。我们报告了整个BMD患者心脏组织中CVPCs（c-kit + / CD45-）显着降低，并且在肌营养不良蛋白缺乏的培养外植体中呈现c-kit阳性的相亮细胞数量减少。此外，离体CVPC的存活率和心脏成纤维细胞迁移显着降低，表明体内稳态支持减少和不可逆组织重构。我们的发现将肌营养不良蛋白缺乏症患者的遗传性心力衰竭与c-kit + / CD45- CVPC降低及其弹性相关联，可能暗示缺乏心脏保护能力和/或体内稳态支持降低。这也与植入的心脏组织的可塑性降低有关，这与BMD患者心脏中不可逆的重塑过程有关。