Nucleoside Diphosphate Kinase B Contributes to Arrhythmogenesis in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with Arrhythmogenic Right Ventricular Cardiomyopathy.

SK4 channel arrhythmia arrhythmogenic right ventricular cardiomyopathy human-induced pluripotent stem cell-derived cardiomyocyte nucleoside diphosphate kinase

Journal

Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588

Informations de publication

Date de publication:
10 Feb 2020
Historique:
received: 08 01 2020
revised: 30 01 2020
accepted: 05 02 2020
entrez: 14 2 2020
pubmed: 14 2 2020
medline: 14 2 2020
Statut: epublish

Résumé

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, inheritable cardiac disorder characterized by ventricular tachyarrhythmias, progressive loss of cardiomyocytes with fibrofatty replacement and sudden cardiac death. The exact underlying mechanisms are unclear. This study investigated the possible roles of nucleoside diphosphate kinase B (NDPK-B) and SK4 channels in the arrhythmogenesis of ARVC by using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In hiPSC-CMs from a patient with ARVC, the expression levels of NDPK-B and SK4 channels were upregulated, the cell automaticity was increased and the occurrence rate of arrhythmic events was enhanced. Recombinant NDPK-B applied into hiPSC-CMs from either healthy donors or the patient enhanced SK4 channel current (I This study demonstrated that the elevated NDPK-B expression, via activating SK4 channels, contributes to arrhythmogenesis in ARVC, and hence, NDPK-B may be a potential therapeutic target for treating arrhythmias in patients with ARVC.

Sections du résumé

BACKGROUND BACKGROUND
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, inheritable cardiac disorder characterized by ventricular tachyarrhythmias, progressive loss of cardiomyocytes with fibrofatty replacement and sudden cardiac death. The exact underlying mechanisms are unclear.
METHODS METHODS
This study investigated the possible roles of nucleoside diphosphate kinase B (NDPK-B) and SK4 channels in the arrhythmogenesis of ARVC by using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
RESULTS RESULTS
In hiPSC-CMs from a patient with ARVC, the expression levels of NDPK-B and SK4 channels were upregulated, the cell automaticity was increased and the occurrence rate of arrhythmic events was enhanced. Recombinant NDPK-B applied into hiPSC-CMs from either healthy donors or the patient enhanced SK4 channel current (I
CONCLUSION CONCLUSIONS
This study demonstrated that the elevated NDPK-B expression, via activating SK4 channels, contributes to arrhythmogenesis in ARVC, and hence, NDPK-B may be a potential therapeutic target for treating arrhythmias in patients with ARVC.

Identifiants

DOI: 10.3390/jcm9020486 PMID: 32050722 PMC: PMC7073527
pubmed: 32050722
pii: jcm9020486
doi: 10.3390/jcm9020486
pmc: PMC7073527
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Deutsches Zentrum für Herz-Kreislaufforschung
ID : 81Z0500204

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Fanis Buljubasic (F)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.

Ibrahim El-Battrawy (I)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.

Huan Lan (H)

Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China.

Santosh K Lomada (SK)

Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

Anupriya Chatterjee (A)

Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

Zhihan Zhao (Z)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.

Xin Li (X)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Rujia Zhong (R)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Qiang Xu (Q)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Mengying Huang (M)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Zhenxing Liao (Z)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.

Siegfried Lang (S)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.

Lukas Cyganek (L)

DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.
Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, 37075 Göttingen, Germany.

Xiaobo Zhou (X)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.
Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China.

Thomas Wieland (T)

DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.
Experimental Pharmacology Mannheim, European Center for Angioscience, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.

Martin Borggrefe (M)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.

Ibrahim Akin (I)

First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
DZHK (German Center for Cardiovascular Research), Partner Sites, Heidelberg-Mannheim and Göttingen, 68167 Mannheim, Germany.

Classifications MeSH