Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, 62500, Czech Republic.
International Clinical Research Center, (ICRC), St. Anne's University Hospital, Pekarska 53, Brno, 65691, Czech Republic.
Orphanet J Rare Dis. 2020 Mar 5;15(1):65. doi: 10.1186/s13023-019-1257-4.
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.
我们描述了贝克型肌营养不良症（BMD）引起的心力衰竭与受影响的心脏组织的组织稳态和重塑能力受损之间的关联。我们报告说，BMD 心力衰竭与心血管祖细胞数量显著减少、心脏成纤维细胞迁移减少以及体外存活能力降低有关。
贝克型肌营养不良症属于一类遗传性肌营养不良症。它影响男性患者，导致进行性骨骼肌退化和扩张型心肌病导致心力衰竭。它是一种相对较轻的肌营养不良症形式，使患者能够进入心脏移植名单。在这种独特的情况下，被移植的心脏是研究肌营养不良症患者心脏组织退行性过程的难得机会。心脏组织被切除、分离并进行分析。比较 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来自健康器官捐献者的心房组织的对照样本。对照组织是在心脏移植手术期间从健康器官捐献者的心脏中获得的。
我们报告说，BMD 患者的整个心脏组织中 CVPC（c-kit/CD45）明显减少，并且在营养不良症的培养外植体中呈现 c-kit 阳性的相亮细胞数量减少。此外，体外 CVPC 存活和心脏成纤维细胞迁移明显减少，表明稳态支持减少和不可逆转的组织重塑。
我们的发现将遗传性心力衰竭与营养不良症患者的 c-kit/CD45 CVPC 减少及其弹性相关联，这可能暗示缺乏心脏保护能力和/或稳态支持减少。这也与 BMD 患者心脏中不可逆转的重塑过程相关的外植心脏组织的可塑性降低相关。
