Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1913 - 1913
Published: Nov. 19, 2024
, encoding cardiac myosin binding protein-C (cMyBP-C), is the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, since little about underlying etiology, additional in vitro studies are crucial defining molecular mechanisms. Accordingly, this study aimed investigate mechanisms pathogenesis of HCM associated with a polymorphic variant (D389V)
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7971 - 7971
Published: July 21, 2024
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype lack of high-throughput analytical methodology. In this study, we developed testing platform utilizing hPSC-CMs to assess the cardiotoxicity effectiveness drugs. Following optimized differentiation maturation protocol, exhibited mature CM morphology, phenotype, functionality, making them suitable applications. We monitored intracellular calcium dynamics using imaging techniques measure spontaneous oscillations in presence or absence test compounds. For test, were treated with various compounds, flux was measured evaluate effects on dynamics. found that cardiotoxic drugs withdrawn due adverse reactions, including encainide, mibefradil, cetirizine, toxicity but not HEK293-hERG cells. Additionally, exposed ATX-II, sodium current inducer mimicking long QT syndrome type 3, followed exposure The observed changes following demonstrated utility versatile model system assessing both efficacy. Overall, our findings highlight potential advancing discovery development, which offer physiologically relevant preclinical screening novel therapeutics.
Language: Английский
Citations
2
Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1913 - 1913
Published: Nov. 19, 2024
, encoding cardiac myosin binding protein-C (cMyBP-C), is the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, since little about underlying etiology, additional in vitro studies are crucial defining molecular mechanisms. Accordingly, this study aimed investigate mechanisms pathogenesis of HCM associated with a polymorphic variant (D389V)
Language: Английский
Citations
1