Abstract
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.BackgroundBecker 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Becker muscular dystrophy belongs to a class of genetically inherited dystrophin deficiencies
Other stromal cells possibly involved in cardiac homeostasis, survival, and disease dynamics are cardiovascular progenitor cells (CVPC) [14], which include the CD117+/ CD45− fraction, and has been the main focus of several recent studies [15, 16]
Due to progressive worsening of dyspnea up to the point of pulmonary edema, which required repeated hospital admissions, the patient was put on the non-urgent heart transplantation waiting list
Summary
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. The cellular dynamics of DCM development in dystrophinopathies are still unclear This condition involves mostly cardiomyocytes, increasing attention has been directed at understanding the features and progression of DCM in the non-muscular cell fractions. These mainly include cardiac fibroblasts [7,8,9] and endothelial. The evidence shows that c-kit+/CD45− are activated by cardiac injury [17] supporting the hypothesis of paracrine regulation of cardiac function under pathophysiological conditions [16, 18, 19]; their role and fate in the human heart remains to be elucidated
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