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Author Spotlight: Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
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Author Spotlight: Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Published on: May 26, 2023

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Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with MYL2-R58Q-Mediated Apical Hypertrophic

Wei Zhou1, J Martijn Bos1,2, Dan Ye1

  • 1Department of Molecular Pharmacology and Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, 55905, USA.

Journal of Cardiovascular Translational Research
|February 24, 2019
PubMed

Insights

A MYL2-R58Q mutation causes hypertrophic cardiomyopathy (HCM) by increasing cardiomyocyte size and disarray. This patient-specific model reveals reduced calcium transients and L-type calcium channel current, offering insights into HCM mechanisms.

Area of Science:

  • Cardiovascular Disease Research
  • Stem Cell Biology
  • Genetic Cardiology

Background:

  • Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease.
  • The MYL2 mutation R58Q is linked to severe HCM and sudden cardiac death (SCD).

Purpose of the Study:

  • To create the first patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model for the MYL2-R58Q mutation.
  • To investigate the cellular and functional consequences of the MYL2-R58Q mutation in iPSC-CMs.

Main Methods:

  • Generation of patient-specific iPSC-CMs carrying the MYL2-R58Q mutation.
  • Assessment of cardiomyocyte size, myofibrillar structure, and beating regularity.
  • Measurement of intracellular calcium transients and L-type Ca2+ channel (LTCC) current.

Main Results:

  • MYL2-R58Q iPSC-CMs exhibited significantly increased cell size (~30%) and myofibrillar disarray.
  • Cells showed higher rates of irregular beating compared to controls.
  • A significant decrease in peak calcium transient amplitude and delayed decay was observed.
  • LTCC current density was reduced by approximately 45.3%.

Conclusions:

  • The MYL2-R58Q iPSC-CM model effectively recapitulates key features of HCM.
  • The mutation leads to cardiac hypertrophy, structural disarray, and altered calcium handling.
  • Unexpectedly, the mutation significantly reduces LTCC function, providing new insights into HCM pathophysiology.

Keywords:
Calcium transientsDisarrayHypertrophic cardiomyopathy (HCM)Induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs)L-type Ca2+ channel (LTCC)Myosin regulatory light chain (MYL2)R58Q

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