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.Základní údaje
Originální název
Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell–Derived Cardiomyocytes
Autoři
KLIMOVIČ, Šimon (203 Česká republika, domácí), Martin ŠČUREK (203 Česká republika, domácí), Martin PEŠL (203 Česká republika, domácí), Deborah BECKEROVÁ (203 Česká republika, domácí), Šárka JELÍNKOVÁ (203 Česká republika, domácí), Tomáš URBAN (203 Česká republika, domácí), Daniil KABANOV (643 Rusko, domácí), Zdeněk STÁREK (203 Česká republika, domácí), Markéta BÉBAROVÁ (203 Česká republika, domácí), Jan PŘIBYL (203 Česká republika, domácí), Vladimír ROTREKL (203 Česká republika, domácí) a Kristián BRAT (703 Slovensko, garant, domácí)
Vydání
Frontiers in Pharmacology, Frontiers Media SA, 2022, 1663-9812
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30402 Technologies involving the manipulation of cells, tissues, organs or the whole organism
Stát vydavatele
Švýcarsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 5.600
Kód RIV
RIV/00216224:14740/22:00125201
Organizační jednotka
Středoevropský technologický institut
UT WoS
000749864500001
Klíčová slova anglicky
aminophylline; IPSC; hESC; cardiomyocytes; drug cardiotoxicity; atomic force microscopy; arrhythmogenic effects; methylxanthines
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 15. 10. 2024 11:13, Ing. Monika Szurmanová, Ph.D.
Anotace
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.
Návaznosti
EF19_073/0016943, projekt VaV |
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LM2018127, projekt VaV |
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MUNI/A/1133/2021, interní kód MU |
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MUNI/A/1246/2020, interní kód MU |
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MUNI/A/1418/2021, interní kód MU |
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MUNI/A/1700/2020, interní kód MU |
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MUNI/IGA/1428/2020, interní kód MU |
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NU20-06-00156, projekt VaV |
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90127, velká výzkumná infrastruktura |
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