Endothelin‐1 Induces Myofibrillar Disarray and Contractile Vector Variability in Hypertrophic Cardiomyopathy–Induced Pluripotent Stem Cell–Derived Cardiomyocytes

Atsushi Tanaka; Shinsuke Yuasa; Giulia Mearini; Toru Egashira; Tomohisa Seki; Masaki Kodaira; Dai Kusumoto; Yusuke Kuroda; Shinichiro Okata; Tomoyuki Suzuki; Taku Inohara; Takuro Arimura; Shinji Makino; Kensuke Kimura; Akinori Kimura; Tetsushi Furukawa; Lucie Carrier; Koichi Node; Keiichi Fukuda

doi:10.1161/jaha.114.001263

Why the study?

Does endothelin-1 induce myofibrillar disarray and contractile vector variability in hypertrophic cardiomyopathy iPSC-derived cardiomyocytes?

Key Points

To determine how endothelin-1 interacts with patient genetic backgrounds to influence pathological structural remodeling and contractile function in hypertrophic cardiomyopathy.
Generated cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) carrying hypertrophic cardiomyopathy genetic backgrounds.
Treated hypertrophic cardiomyopathy iPSC-CMs with endothelin-1 to evaluate cellular organization and contractile mechanics.
Endothelin-1 exposure promoted the pathological hypertrophic cardiomyopathy phenotype in patient-derived cardiomyocytes.
Treatment induced myofibrillar disarray and increased contractile vector variability via interactions between patient genetics and endothelin-1.

Structured PICO

Does endothelin-1 induce myofibrillar disarray and contractile vector variability in hypertrophic cardiomyopathy iPSC-derived cardiomyocytes?

P

Population

Hypertrophic cardiomyopathy (HCM) induced pluripotent stem cell (iPSC)-derived cardiomyocytes

I

Intervention

Endothelin-1

O

Outcome

HCM pathological phenotype, myofibrillar disarray, and contractile variabilitysurrogate

Endothelin-1 interacts with genetic backgrounds to promote pathological phenotypes and contractile variability in in vitro models of hypertrophic cardiomyopathy.

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Implication

Does not support endothelin-1 targeting in HCM; leaves open clinical translation of iPSC gene-environment findings.

Abstract

Interactions between the patient's genetic backgrounds and the environmental factor endothelin-1 promote the HCM pathological phenotype and contractile variability in the HCM iPSC-derived cardiomyocytes.

Discussion

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Cite This Study

Tanaka et al. (2014) studied this question.

synapsesocial.com/papers/69d572e975589c71d767e907 https://doi.org/10.1161/jaha.114.001263

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Endothelin‐1 Induces Myofibrillar Disarray and Contractile Vector Variability in Hypertrophic Cardiomyopathy–Induced Pluripotent Stem Cell–Derived Cardiomyocytes

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Endothelin‐1 Induces Myofibrillar Disarray and Contractile Vector Variability in Hypertrophic Cardiomyopathy–Induced Pluripotent Stem Cell–Derived Cardiomyocytes

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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