Cardiovascular progenitor cells and tissue plasticity are reduced in a myocardium affected by Becker muscular dystrophy.
Orphanet J Rare Dis. 2020-03-05; 15(1):
DOI: 10.1186/s13023-019-1257-4
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Pesl M(1)(2)(3), Jelinkova S(1)(2), Caluori G(2)(4), Holicka M(5), Krejci J(3), Nemec P(6), Kohutova A(1)(2), Zampachova V(7), Dvorak P(1), Rotrekl V(8)(9).
Author information:
(1)Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, 62500, Czech Republic.
(2)International Clinical Research Center, (ICRC), St. Anne’s University Hospital, Pekarska 53, Brno, 65691, Czech Republic.
(3)1st Department of Cardiovascular Diseases, St. Anne’s University Hospital and Masaryk University, Pekarska 53, Brno, 65691, Czech Republic.
(4)Central European Institute of Technology (CEITEC MU), Nanobiotechnology, Kamenice 5, Brno, 62500, Czech Republic.
(5)Department of Cardiology, University Hospital Brno, Jihlavska 20, Brno, 62500, Czech Republic.
(6)Center for Cardiovascular Surgery and Transplantation, Pekarska 53, Brno, 65691, Czech Republic.
(7)1st Department of Pathology, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital in Brno, Pekarska 53, Brno, 65691, Czech Republic.
(8)Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, 62500, Czech Republic. .
(9)International Clinical Research Center, (ICRC), St. Anne’s University Hospital, Pekarska 53, Brno, 65691, Czech Republic. .
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.BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.