YAP1 reactivation in cardiomyocytes following ECM remodelling
contributes to the development of contractile force and
sarcomere maturation

J 2025

YAP1 reactivation in cardiomyocytes following ECM remodelling contributes to the development of contractile force and sarcomere maturation

VINARSKÝ, Vladimír; Stefania PAGLIARI; Bacel ALDABASH; Fabiana MARTINO; Cristina MAZZOTTI et al.

Základní údaje

Originální název

YAP1 reactivation in cardiomyocytes following ECM remodelling contributes to the development of contractile force and sarcomere maturation

Autoři

Vydání

CELL DEATH DISCOVERY, London, SPRINGERNATURE, 2025, 2058-7716

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.000 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00142817

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

YAP1; cardiomyocytes; extracellular matrix remodelling; sarcomere maturation; contractile force

Štítky

14110132, CF CELLIM, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 3. 2026 11:45, Mgr. Tereza Miškechová

Anotace

V originále

Cardiac diseases are fueled by extracellular matrix (ECM) remodelling. Together with the altered ECM chemical composition, the mechanical turmoil associated with ECM maladaptive remodelling in the pathological heart drives the shuttling of Yes Associated Protein 1 (YAP1) into cardiomyocyte (CM) nuclei that results either in cell cycle re-entry or cardiomyocyte hypertrophy. The mechanism of YAP1 reactivation and factors driving qualitatively different cellular outcomes is not well understood. Here we employed mechanical actuation as a proxy reproducing ECM remodelling in vitro to trigger YAP1 nuclear shuttling in contractile cardiomyocytes derived from human embryonic and induced pluripotent stem cells (hPSCs). By using hPSC lines in which YAP1 expression has been genetically depleted, super-resolution microscopy and electrophysiological measurements, we show that ECM-triggered nuclear presence of endogenous YAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of their electrophysiological properties and calcium dynamics. We eventually exploit engineered heart tissues (EHTs) to demonstrate that the net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth that results in reduced force development. These results suggest that the re-activation of endogenous YAP1 following ECM maladaptive remodelling promotes cardiomyocyte contractility by restructuring the sarcomere apparatus and the maturation of electrophysiological properties via transcriptionally dependent and independent mechanisms.

Návaznosti

MUNI/A/1760/2024, interní kód MU

Název: Biomedicínské vědy V

Investor: Masarykova univerzita, Biomedicínské vědy V

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging III

Citovat

VINARSKÝ, Vladimír; Stefania PAGLIARI; Bacel ALDABASH; Fabiana MARTINO; Cristina MAZZOTTI; Katerina JIRAKOVA; Zuzana GARLIKOVA; Di Iuri ENRICO; Daniel KYTYR; Patrizia BENZONI; Martina ARICI; Alessia METALLO; Kira ZEEVAERT; Wolfgang WAGNER; Marcella ROCCHETTI a Giancarlo FORTE. YAP1 reactivation in cardiomyocytes following ECM remodelling contributes to the development of contractile force and sarcomere maturation. CELL DEATH DISCOVERY. London: SPRINGERNATURE, 2025, roč. 11, č. 1, s. 1-14. ISSN 2058-7716. Dostupné z: https://doi.org/10.1038/s41420-025-02793-2.

@article{2537804,
   author = {Vinarský, Vladimír and Pagliari, Stefania and Aldabash, Bacel and Martino, Fabiana and Mazzotti, Cristina and Jirakova, Katerina and Garlikova, Zuzana and Enrico, Di Iuri and Kytyr, Daniel and Benzoni, Patrizia and Arici, Martina and Metallo, Alessia and Zeevaert, Kira and Wagner, Wolfgang and Rocchetti, Marcella and Forte, Giancarlo},
   article_location = {London},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41420-025-02793-2},
   keywords = {YAP1; cardiomyocytes; extracellular matrix remodelling; sarcomere maturation; contractile force},
   language = {eng},
   issn = {2058-7716},
   journal = {CELL DEATH DISCOVERY},
   title = {YAP1 reactivation in cardiomyocytes following ECM remodelling contributes to the development of contractile force and sarcomere maturation},
   url = {https://pubmed.ncbi.nlm.nih.gov/41213910/},
   volume = {11},
   year = {2025}
}

TY  - JOUR
ID  - 2537804
AU  - Vinarský, Vladimír - Pagliari, Stefania - Aldabash, Bacel - Martino, Fabiana - Mazzotti, Cristina - Jirakova, Katerina - Garlikova, Zuzana - Enrico, Di Iuri - Kytyr, Daniel - Benzoni, Patrizia - Arici, Martina - Metallo, Alessia - Zeevaert, Kira - Wagner, Wolfgang - Rocchetti, Marcella - Forte, Giancarlo
PY  - 2025
TI  - YAP1 reactivation in cardiomyocytes following ECM remodelling contributes to the development of contractile force and sarcomere maturation
JF  - CELL DEATH DISCOVERY
VL  - 11
IS  - 1
SP  - 1-14
EP  - 1-14
PB  - SPRINGERNATURE
SN  - 20587716
KW  - YAP1
KW  - cardiomyocytes
KW  - extracellular matrix remodelling
KW  - sarcomere maturation
KW  - contractile force
UR  - https://pubmed.ncbi.nlm.nih.gov/41213910/
N2  - Cardiac diseases are fueled by extracellular matrix (ECM) remodelling. Together with the altered ECM chemical composition, the mechanical turmoil associated with ECM maladaptive remodelling in the pathological heart drives the shuttling of Yes Associated Protein 1 (YAP1) into cardiomyocyte (CM) nuclei that results either in cell cycle re-entry or cardiomyocyte hypertrophy. The mechanism of YAP1 reactivation and factors driving qualitatively different cellular outcomes is not well understood. Here we employed mechanical actuation as a proxy reproducing ECM remodelling in vitro to trigger YAP1 nuclear shuttling in contractile cardiomyocytes derived from human embryonic and induced pluripotent stem cells (hPSCs). By using hPSC lines in which YAP1 expression has been genetically depleted, super-resolution microscopy and electrophysiological measurements, we show that ECM-triggered nuclear presence of endogenous YAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of their electrophysiological properties and calcium dynamics. We eventually exploit engineered heart tissues (EHTs) to demonstrate that the net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth that results in reduced force development. These results suggest that the re-activation of endogenous YAP1 following ECM maladaptive remodelling promotes cardiomyocyte contractility by restructuring the sarcomere apparatus and the maturation of electrophysiological properties via transcriptionally dependent and independent mechanisms.
ER  -

VINARSKÝ, Vladimír; Stefania PAGLIARI; Bacel ALDABASH; Fabiana MARTINO; Cristina MAZZOTTI; Katerina JIRAKOVA; Zuzana GARLIKOVA; Di Iuri ENRICO; Daniel KYTYR; Patrizia BENZONI; Martina ARICI; Alessia METALLO; Kira ZEEVAERT; Wolfgang WAGNER; Marcella ROCCHETTI a Giancarlo FORTE. YAP1 reactivation in cardiomyocytes following ECM remodelling contributes to the development of contractile force and sarcomere maturation. \textit{CELL DEATH DISCOVERY}. London: SPRINGERNATURE, 2025, roč.~11, č.~1, s.~1-14. ISSN~2058-7716. Dostupné z: https://doi.org/10.1038/s41420-025-02793-2.

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