CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS
JEP ZA	1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S
IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces
Two Types of Arrhythmic Events in Human Pluripotent Stem
Cell–Derived Cardiomyocytes

o 2023

CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP ZA 1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes

KLIMOVIČ, Šimon, Martin ŠČUREK, Martin PEŠL, Deborah BECKEROVÁ, Šárka JELÍNKOVÁ et. al.

Basic information

Original name

CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP ZA 1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes

Authors

Edition

2023

Publisher

VÝBOR ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP

Other information

Language

English

Type of outcome

Ocenění vědecké a umělecké činnosti

Field of Study

30402 Technologies involving the manipulation of cells, tissues, organs or the whole organism

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Organization unit

Central European Institute of Technology

Keywords in English

aminophylline; IPSC; hESC; cardiomyocytes; drug cardiotoxicity; atomic force microscopy; arrhythmogenic effects; methylxanthines

Abstract

V originále

Cardiac side effects of some pulmonary drugs are observed in clinical practice. Aminophylline, a methylxanthine bronchodilator with documented proarrhythmic action, may serve as an example. Data on the action of aminophylline on cardiac cell electrophysiology and contractility are not available. Hence, this study was focused on the analysis of changes in the beat rate and contraction force of human pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes in the presence of increasing concentrations of aminophylline (10 µM–10 mM in hPSC-CM and 8–512 µM in HL-1 cardiomyocytes). Basic biomedical parameters, namely, the beat rate (BR) and contraction force, were assessed in hPSC-CMs using an atomic force microscope (AFM). The beat rate changes under aminophylline were also examined on the HL-1 cardiac muscle cell line via a multielectrode array (MEA). Additionally, calcium imaging was used to evaluate the effect of aminophylline on intracellular Ca2+ dynamics in HL-1 cardiomyocytes. The BR was significantly increased after the application of aminophylline both in hPSC-CMs (with 10 mM aminophylline) and in HL-1 cardiomyocytes (with 256 and 512 µM aminophylline) in comparison with controls. A significant increase in the contraction force was also observed in hPSC-CMs with 10 µM aminophylline (a similar trend was visible at higher concentrations as well). We demonstrated that all aminophylline concentrations significantly increased the frequency of rhythm irregularities (extreme interbeat intervals) both in hPSC-CMs and HL-1 cells. The occurrence of the calcium sparks in HL-1 cardiomyocytes was significantly increased with the presence of 512 µM aminophylline. We conclude that the observed aberrant cardiomyocyte response to aminophylline suggests an arrhythmogenic potential of the drug. The acquired data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and describe cellular mechanisms of methylxanthine arrhythmogenesis. An AFM combined with hPSC-CMs may serve as a robust platform for direct drug effect screening.

Links

EF19_073/0016943, research and development project

Name: Interní grantová agentura Masarykovy univerzity

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1133/2021, interní kód MU

Name: Od buňky k medicíně (Acronym: CELLVIEW)

Investor: Masaryk University

MUNI/A/1246/2020, interní kód MU

Name: Kardiovaskulární systém: od iontového kanálu k celotělovému modelu (Acronym: KAVASYKAMO)

Investor: Masaryk University

MUNI/A/1418/2021, interní kód MU

Name: Biomedicínské vědy II (Acronym: BIOMED)

Investor: Masaryk University

MUNI/A/1700/2020, interní kód MU

Name: Stop and go efekt aminophyllinu a stanovení hladin běžně užívaných bronchodilatancií v plazmě

Investor: Masaryk University

MUNI/IGA/1428/2020, interní kód MU

Name: Characterization of cardiovascular progenitor population during development (Acronym: cardioprogenitors)

Investor: Masaryk University

NU20-06-00156, research and development project

Name: Vliv pneumologické medikace na funkce lidských kardiomyocytů.

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Citovat

KLIMOVIČ, Šimon, Martin ŠČUREK, Martin PEŠL, Deborah BECKEROVÁ, Šárka JELÍNKOVÁ, Tomáš URBAN, Daniil KABANOV, Zdeněk STÁREK, Markéta BÉBAROVÁ, Jan PŘIBYL, Vladimír ROTREKL and Kristián BRAT. CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP ZA 1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes. VÝBOR ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP, 2023.

@misc{2339517,
   author = {Klimovič, Šimon and Ščurek, Martin and Pešl, Martin and Beckerová, Deborah and Jelínková, Šárka and Urban, Tomáš and Kabanov, Daniil and Stárek, Zdeněk and Bébarová, Markéta and Přibyl, Jan and Rotrekl, Vladimír and Brat, Kristián},
   keywords = {aminophylline; IPSC; hESC; cardiomyocytes; drug cardiotoxicity; atomic force microscopy; arrhythmogenic effects; methylxanthines},
   language = {eng},
   publisher = {VÝBOR ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP},
   title = {CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP ZA 1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes},
   url = {https://www.plicnilekarstvi.cz/novinka/2320/publikacni-souteze-cpfs-za-rok-2022-znaji-viteze/},
   year = {2023}
}

TY  - GEN
ID  - 2339517
AU  - Klimovič, Šimon - Ščurek, Martin - Pešl, Martin - Beckerová, Deborah - Jelínková, Šárka - Urban, Tomáš - Kabanov, Daniil - Stárek, Zdeněk - Bébarová, Markéta - Přibyl, Jan - Rotrekl, Vladimír - Brat, Kristián
PY  - 2023
TI  - CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP ZA 1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes
PB  - VÝBOR ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP
KW  - aminophylline
KW  - IPSC
KW  - hESC
KW  - cardiomyocytes
KW  - drug cardiotoxicity
KW  - atomic force microscopy
KW  - arrhythmogenic effects
KW  - methylxanthines
UR  - https://www.plicnilekarstvi.cz/novinka/2320/publikacni-souteze-cpfs-za-rok-2022-znaji-viteze/
N2  - Cardiac side effects of some pulmonary drugs are observed in clinical practice. Aminophylline, a methylxanthine bronchodilator with documented proarrhythmic action, may serve as an example. Data on the action of aminophylline on cardiac cell electrophysiology and contractility are not available. Hence, this study was focused on the analysis of changes in the beat rate and contraction force of human pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes in the presence of increasing concentrations of aminophylline (10 µM–10 mM in hPSC-CM and 8–512 µM in HL-1 cardiomyocytes). Basic biomedical parameters, namely, the beat rate (BR) and contraction force, were assessed in hPSC-CMs using an atomic force microscope (AFM). The beat rate changes under aminophylline were also examined on the HL-1 cardiac muscle cell line via a multielectrode array (MEA). Additionally, calcium imaging was used to evaluate the effect of aminophylline on intracellular Ca2+ dynamics in HL-1 cardiomyocytes. The BR was significantly increased after the application of aminophylline both in hPSC-CMs (with 10 mM aminophylline) and in HL-1 cardiomyocytes (with 256 and 512 µM aminophylline) in comparison with controls. A significant increase in the contraction force was also observed in hPSC-CMs with 10 µM aminophylline (a similar trend was visible at higher concentrations as well). We demonstrated that all aminophylline concentrations significantly increased the frequency of rhythm irregularities (extreme interbeat intervals) both in hPSC-CMs and HL-1 cells. The occurrence of the calcium sparks in HL-1 cardiomyocytes was significantly increased with the presence of 512 µM aminophylline. We conclude that the observed aberrant cardiomyocyte response to aminophylline suggests an arrhythmogenic potential of the drug. The acquired data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and describe cellular mechanisms of methylxanthine arrhythmogenesis. An AFM combined with hPSC-CMs may serve as a robust platform for direct drug effect screening.
ER  -

KLIMOVIČ, Šimon, Martin ŠČUREK, Martin PEŠL, Deborah BECKEROVÁ, Šárka JELÍNKOVÁ, Tomáš URBAN, Daniil KABANOV, Zdeněk STÁREK, Markéta BÉBAROVÁ, Jan PŘIBYL, Vladimír ROTREKL and Kristián BRAT. \textit{CENA VÝBORU ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP ZA 1. NEJLEPŠÍ PUBLIKOVANOU PRÁCI V KATEGORII PUBLIKACE S IMPAKT FAKTOREM POD 35 LET V ROCE 2022: Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes}. VÝBOR ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP, 2023.

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