Cardiac progenitors in Duchenne muscular dystrophy show
elevated DNA damage and accelerated maturation

a 2026

Cardiac progenitors in Duchenne muscular dystrophy show elevated DNA damage and accelerated maturation

BECKEROVÁ, Deborah; Martin PEŠL; Hana DOBROVOLNÁ a Vladimír ROTREKL

Základní údaje

Originální název

Cardiac progenitors in Duchenne muscular dystrophy show elevated DNA damage and accelerated maturation

Autoři

BECKEROVÁ, Deborah; Martin PEŠL; Hana DOBROVOLNÁ a Vladimír ROTREKL

Vydání

EMBL Conference: The new cardiobiology: engineering, vascular, and molecular insights, 2026

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Odkazy

URL

Označené pro přenos do RIV

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Duchenne muscular dystrophy; cardiac organoid; cardiovascular progenitor

Změněno: 23. 2. 2026 13:46, Mgr. Bc. Deborah Beckerová

Anotace

V originále

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disorder caused by dystrophin mutations, which result in progressive skeletal muscle loss followed by cardiomyopathy. Current medical care is palliative; interventions and improved therapies require further research. We previously showed that DMD already affects the pluripotent stem cell (PSC) stage through elevated DNA damage and mutagenesis, at least partially caused by deregulated nitric oxide synthase (NOS) and production of reactive species. Given these results, we questioned how that affects cardiac tissue development. DMD cardiovascular progenitor (CP) population in developing cardiac organoids shows an altered transcriptional program during differentiation. CP markers activate earlier, followed by earlier onset of maturation-related gene expression and ongoing inflammation. DMD CPs present higher levels of DNA damage and lowered proliferation. These early deregulations are followed by impaired cardiac differentiation efficacy with higher rate of cardiomyocyte (CM) death as well as increased and accelerated collagen deposition, thus recapitulating the phenotype of mdx mouse and human DMD hearts. NOS inhibition attenuates DNA damage in CPs, rescues CP proliferation and improves formation of beating organoids; however, it does not prevent CM death or significantly affect transcription of cardiac development-related genes. Thus, with further study, NOS inhibition may complement current medical care. Project was funded by project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) – Funded by the European Union – Next Generation EU.

Návaznosti

LX22NPO5104, projekt VaV

Název: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění (Akronym: CarDia)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní institut pro léčbu metabolických a kardiovaskulárních onemocnění, 5.1 EXCELES

Citovat

BECKEROVÁ, Deborah; Martin PEŠL; Hana DOBROVOLNÁ a Vladimír ROTREKL. Cardiac progenitors in Duchenne muscular dystrophy show elevated DNA damage and accelerated maturation. In EMBL Conference: The new cardiobiology: engineering, vascular, and molecular insights. 2026.

@proceedings{2556240,
   author = {Beckerová, Deborah and Pešl, Martin and Dobrovolná, Hana and Rotrekl, Vladimír},
   booktitle = {EMBL Conference: The new cardiobiology: engineering, vascular, and molecular insights},
   keywords = {Duchenne muscular dystrophy; cardiac organoid; cardiovascular progenitor},
   language = {eng},
   title = {Cardiac progenitors in Duchenne muscular dystrophy show elevated DNA damage and accelerated maturation},
   url = {https://is.muni.cz/auth/publication/2556157/5MEa2ZXJTSfAafY8bFQi_2_full.pdf},
   year = {2026}
}

TY  - CONF
ID  - 2556240
AU  - Beckerová, Deborah - Pešl, Martin - Dobrovolná, Hana - Rotrekl, Vladimír
PY  - 2026
TI  - Cardiac progenitors in Duchenne muscular dystrophy show elevated DNA damage and accelerated maturation
KW  - Duchenne muscular dystrophy
KW  - cardiac organoid
KW  - cardiovascular progenitor
UR  - https://is.muni.cz/auth/publication/2556157/5MEa2ZXJTSfAafY8bFQi_2_full.pdf
N2  - Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disorder caused by dystrophin mutations, which result in progressive skeletal muscle loss followed by cardiomyopathy. Current medical care is palliative; interventions and improved therapies require further research. We previously showed that DMD already affects the pluripotent stem cell (PSC) stage through elevated DNA damage and mutagenesis, at least partially caused by deregulated nitric oxide synthase (NOS) and production of reactive species. Given these results, we questioned how that affects cardiac tissue development. DMD cardiovascular progenitor (CP) population in developing cardiac organoids shows an altered transcriptional program during differentiation. CP markers activate earlier, followed by earlier onset of maturation-related gene expression and ongoing inflammation. DMD CPs present higher levels of DNA damage and lowered proliferation. These early deregulations are followed by impaired cardiac differentiation efficacy with higher rate of cardiomyocyte (CM) death as well as increased and accelerated collagen deposition, thus recapitulating the phenotype of mdx mouse and human DMD hearts. NOS inhibition attenuates DNA damage in CPs, rescues CP proliferation and improves formation of beating organoids; however, it does not prevent CM death or significantly affect transcription of cardiac development-related genes. Thus, with further study, NOS inhibition may complement current medical care. Project was funded by project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) – Funded by the European Union – Next Generation EU.
ER  -

BECKEROVÁ, Deborah; Martin PEŠL; Hana DOBROVOLNÁ a Vladimír ROTREKL. Cardiac progenitors in Duchenne muscular dystrophy show elevated DNA damage and accelerated maturation. In \textit{EMBL Conference: The new cardiobiology: engineering, vascular, and molecular insights}. 2026.

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