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.
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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 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.
Edition 2023.
Publisher VÝBOR ČESKÉ PNEUMOLOGICKÉ A FTIZEOLOGICKÉ SPOLEČNOSTI ČLS JEP
Other information
Original language English
Type of outcome Scientific or artistic work award
Field of Study 30402 Technologies involving the manipulation of cells, tissues, organs or the whole organism
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Organization unit Central European Institute of Technology
Keywords in English aminophylline; IPSC; hESC; cardiomyocytes; drug cardiotoxicity; atomic force microscopy; arrhythmogenic effects; methylxanthines
Tags International impact, Reviewed
Changed by Changed by: MUDr. Martin Pešl, Ph.D., učo 60014. Changed: 15/11/2023 08:21.
Abstract
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 projectName: Interní grantová agentura Masarykovy univerzity
LM2018127, research and development projectName: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1133/2021, interní kód MUName: Od buňky k medicíně (Acronym: CELLVIEW)
Investor: Masaryk University
MUNI/A/1246/2020, interní kód MUName: Kardiovaskulární systém: od iontového kanálu k celotělovému modelu (Acronym: KAVASYKAMO)
Investor: Masaryk University
MUNI/A/1418/2021, interní kód MUName: Biomedicínské vědy II (Acronym: BIOMED)
Investor: Masaryk University
MUNI/A/1700/2020, interní kód MUName: Stop and go efekt aminophyllinu a stanovení hladin běžně užívaných bronchodilatancií v plazmě
Investor: Masaryk University
MUNI/IGA/1428/2020, interní kód MUName: Characterization of cardiovascular progenitor population during development (Acronym: cardioprogenitors)
Investor: Masaryk University
NU20-06-00156, research and development projectName: Vliv pneumologické medikace na funkce lidských kardiomyocytů.
Investor: Ministry of Health of the CR, Subprogram 1 - standard
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