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Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy

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Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. / Paavola, Jere; Schliffke, Simon; Rossetti, Sandro; Kuo, Ivana Y-T; Yuan, Shiaulou; Sun, Zhaoxia; Harris, Peter C; Torres, Vicente E; Ehrlich, Barbara E.

in: J MOL CELL CARDIOL, Jahrgang 58, 01.05.2013, S. 199-208.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Paavola, J, Schliffke, S, Rossetti, S, Kuo, IY-T, Yuan, S, Sun, Z, Harris, PC, Torres, VE & Ehrlich, BE 2013, 'Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy', J MOL CELL CARDIOL, Jg. 58, S. 199-208. https://doi.org/10.1016/j.yjmcc.2013.01.015

APA

Paavola, J., Schliffke, S., Rossetti, S., Kuo, I. Y-T., Yuan, S., Sun, Z., Harris, P. C., Torres, V. E., & Ehrlich, B. E. (2013). Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. J MOL CELL CARDIOL, 58, 199-208. https://doi.org/10.1016/j.yjmcc.2013.01.015

Vancouver

Paavola J, Schliffke S, Rossetti S, Kuo IY-T, Yuan S, Sun Z et al. Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. J MOL CELL CARDIOL. 2013 Mai 1;58:199-208. https://doi.org/10.1016/j.yjmcc.2013.01.015

Bibtex

@article{26c751ba433444d19b8fb27d95e03eb8,
title = "Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy",
abstract = "Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2), cause autosomal dominant polycystic kidney disease (ADPKD). Although the leading cause of mortality in ADPKD is cardiovascular disease, the relationship between these conditions remains poorly understood. PC2 is an intracellular calcium channel expressed in renal epithelial cells and in cardiomyocytes, and is thus hypothesized to modulate intracellular calcium signaling and affect cardiac function. Our first aim was to study cardiac function in a zebrafish model lacking PC2 (pkd2 mutants). Next, we aimed to explore the relevance of this zebrafish model to human ADPKD by examining the Mayo Clinic's ADPKD database for an association between ADPKD and idiopathic dilated cardiomyopathy (IDCM). Pkd2 mutant zebrafish showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. In human ADPKD patients, we found IDCM to coexist frequently with ADPKD. This association was strongest in patients with PKD2 mutations. Our results demonstrate that PC2 modulates intracellular calcium cycling, contributing to the development of heart failure. In human subjects we found an association between ADPKD and IDCM and suggest that PKD mutations contribute to the development of heart failure.",
keywords = "Animals, Calcium, Calcium Signaling, Cardiomyopathy, Dilated, Carrier Proteins, Genetic Predisposition to Disease, Humans, Myocytes, Cardiac, Podocytes, Polycystic Kidney, Autosomal Dominant, TRPP Cation Channels, Zebrafish, Zebrafish Proteins",
author = "Jere Paavola and Simon Schliffke and Sandro Rossetti and Kuo, {Ivana Y-T} and Shiaulou Yuan and Zhaoxia Sun and Harris, {Peter C} and Torres, {Vicente E} and Ehrlich, {Barbara E}",
note = "Copyright {\textcopyright} 2013 Elsevier Ltd. All rights reserved.",
year = "2013",
month = may,
day = "1",
doi = "10.1016/j.yjmcc.2013.01.015",
language = "English",
volume = "58",
pages = "199--208",
journal = "J MOL CELL CARDIOL",
issn = "0022-2828",
publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy

AU - Paavola, Jere

AU - Schliffke, Simon

AU - Rossetti, Sandro

AU - Kuo, Ivana Y-T

AU - Yuan, Shiaulou

AU - Sun, Zhaoxia

AU - Harris, Peter C

AU - Torres, Vicente E

AU - Ehrlich, Barbara E

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2), cause autosomal dominant polycystic kidney disease (ADPKD). Although the leading cause of mortality in ADPKD is cardiovascular disease, the relationship between these conditions remains poorly understood. PC2 is an intracellular calcium channel expressed in renal epithelial cells and in cardiomyocytes, and is thus hypothesized to modulate intracellular calcium signaling and affect cardiac function. Our first aim was to study cardiac function in a zebrafish model lacking PC2 (pkd2 mutants). Next, we aimed to explore the relevance of this zebrafish model to human ADPKD by examining the Mayo Clinic's ADPKD database for an association between ADPKD and idiopathic dilated cardiomyopathy (IDCM). Pkd2 mutant zebrafish showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. In human ADPKD patients, we found IDCM to coexist frequently with ADPKD. This association was strongest in patients with PKD2 mutations. Our results demonstrate that PC2 modulates intracellular calcium cycling, contributing to the development of heart failure. In human subjects we found an association between ADPKD and IDCM and suggest that PKD mutations contribute to the development of heart failure.

AB - Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2), cause autosomal dominant polycystic kidney disease (ADPKD). Although the leading cause of mortality in ADPKD is cardiovascular disease, the relationship between these conditions remains poorly understood. PC2 is an intracellular calcium channel expressed in renal epithelial cells and in cardiomyocytes, and is thus hypothesized to modulate intracellular calcium signaling and affect cardiac function. Our first aim was to study cardiac function in a zebrafish model lacking PC2 (pkd2 mutants). Next, we aimed to explore the relevance of this zebrafish model to human ADPKD by examining the Mayo Clinic's ADPKD database for an association between ADPKD and idiopathic dilated cardiomyopathy (IDCM). Pkd2 mutant zebrafish showed low cardiac output and atrioventricular block. Isolated pkd2 mutant hearts displayed impaired intracellular calcium cycling and calcium alternans. These results indicate heart failure in the pkd2 mutants. In human ADPKD patients, we found IDCM to coexist frequently with ADPKD. This association was strongest in patients with PKD2 mutations. Our results demonstrate that PC2 modulates intracellular calcium cycling, contributing to the development of heart failure. In human subjects we found an association between ADPKD and IDCM and suggest that PKD mutations contribute to the development of heart failure.

KW - Animals

KW - Calcium

KW - Calcium Signaling

KW - Cardiomyopathy, Dilated

KW - Carrier Proteins

KW - Genetic Predisposition to Disease

KW - Humans

KW - Myocytes, Cardiac

KW - Podocytes

KW - Polycystic Kidney, Autosomal Dominant

KW - TRPP Cation Channels

KW - Zebrafish

KW - Zebrafish Proteins

U2 - 10.1016/j.yjmcc.2013.01.015

DO - 10.1016/j.yjmcc.2013.01.015

M3 - SCORING: Journal article

C2 - 23376035

VL - 58

SP - 199

EP - 208

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

ER -