Patient-Derived hiPSC-Cardiomyocytes and Engineered Heart Tissues Reveal Distinct Functional Phenotypes in Inherited Cardiomyopathies
Pohjavaara, S. A.; Majid, Q. A.; Huttunen, L.; Aalto-Setälä, K.; Ruskoaho, H.; Välimäki, M. J.; Kinnunen, S. M.; Talman, V. · pharmacology and toxicology · 2026-09-04 · 原文
DOI：10.64898/2026.08.28.747951作者：8 位
Background Hypertrophic and dilated cardiomyopathies (HCM and DCM) are the most common inherited cardiomyopathies. However, genotype-specific molecular and functional cardiomyocyte phenotypes and responses to neurohormonal stimulation remain incompletely understood. Here, we investigated whether patient-derived HCM and DCM cardiomyocytes exhibit distinct baseline phenotypes or differential responses to hypertrophic stimulation and pharmacological treatment. Methods Three human-induced pluripotent stem cell (hiPSC) lines were used: a control line, an HCM patient-derived line carrying a MYBPC3 mutation, and a DCM patient-derived line carrying an LMNA mutation. The cells were differentiated into hiPSC-cardiomyocytes, which were exposed to endothelin-1 and the GATA4-targeted compound 3i-1262, followed by transcriptional and protein expression analyses. In addition, engineered heart tissues (EHTs) were generated and cultured for 40 days, with endothelin-1 and 3i-1262 treatment applied during the final 20 days. Lastly, {beta}-adrenergic stimulation with isoprenaline was performed. EHT contractile function was quantified using MUSCLEMOTION. Results Patient-derived hiPSC-cardiomyocytes exh
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1. 人话版
Background Hypertrophic and dilated cardiomyopathies (HCM and DCM) are the most common inherited cardiomyopathies.
However, genotype-specific molecular and functional cardiomyocyte phenotypes and responses to neurohormonal stimulation remain incompletely understood.
2. 领域脉络
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3. 机制拆解
Here, we investigated whether patient-derived HCM and DCM cardiomyocytes exhibit distinct baseline phenotypes or differential responses to hypertrophic stimulation and pharmacological treatment.
4. 证据与数字
Methods Three human-induced pluripotent stem cell (hiPSC) lines were used: a control line, an HCM patient-derived line carrying a MYBPC3 mutation, and a DCM patient-derived line carrying an LMNA mutation.
The cells were differentiated into hiPSC-cardiomyocytes, which were exposed to endothelin-1 and the GATA4-targeted compound 3i-1262, followed by transcriptional and protein expression analyses.
In addition, engineered heart tissues (EHTs) were generated and cultured for 40 days, with endothelin-1 and 3i-1262 treatment applied during the final 20 days.
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