PortalPublikationenCRISPLD1: a novel conserved target in the transition to huma...

CRISPLD1: a novel conserved target in the transition to human heart failure

Standard

CRISPLD1: a novel conserved target in the transition to human heart failure. / Khadjeh, Sara; Hindmarsh, Vanessa; Weber, Frederike; Cyganek, Lukas; Vidal, Ramon O; Torkieh, Setare; Streckfuss-Bömeke, Katrin; Lbik, Dawid; Tiburcy, Malte; Mohamed, Belal A; Bonn, Stefan; Toischer, Karl; Hasenfuss, Gerd.

in: BASIC RES CARDIOL, Jahrgang 115, Nr. 3, 07.03.2020, S. 27.

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

Harvard

Khadjeh, S, Hindmarsh, V, Weber, F, Cyganek, L, Vidal, RO, Torkieh, S, Streckfuss-Bömeke, K, Lbik, D, Tiburcy, M, Mohamed, BA, Bonn, S, Toischer, K & Hasenfuss, G 2020, 'CRISPLD1: a novel conserved target in the transition to human heart failure', BASIC RES CARDIOL, Jg. 115, Nr. 3, S. 27. https://doi.org/10.1007/s00395-020-0784-4

APA

Khadjeh, S., Hindmarsh, V., Weber, F., Cyganek, L., Vidal, R. O., Torkieh, S., Streckfuss-Bömeke, K., Lbik, D., Tiburcy, M., Mohamed, B. A., Bonn, S., Toischer, K., & Hasenfuss, G. (2020). CRISPLD1: a novel conserved target in the transition to human heart failure. BASIC RES CARDIOL, 115(3), 27. https://doi.org/10.1007/s00395-020-0784-4

Vancouver

Khadjeh S, Hindmarsh V, Weber F, Cyganek L, Vidal RO, Torkieh S et al. CRISPLD1: a novel conserved target in the transition to human heart failure. BASIC RES CARDIOL. 2020 Mär 7;115(3):27. https://doi.org/10.1007/s00395-020-0784-4

Bibtex

@article{e4a6df8538084a66bffd076466d34002,
title = "CRISPLD1: a novel conserved target in the transition to human heart failure",
abstract = "Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca2+ regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions.",
keywords = "Amino Acid Sequence, Animals, Aortic Valve Stenosis/complications, Apoptosis, Biopsy, Calcium/metabolism, Calcium Signaling, Cell Adhesion Molecules/chemistry, Conserved Sequence, Down-Regulation, Evolution, Molecular, Female, Heart Failure/complications, Humans, Induced Pluripotent Stem Cells/cytology, Male, Mice, Myocardium/metabolism, Myocytes, Cardiac/cytology, Transcriptome, Transforming Growth Factor beta/metabolism",
author = "Sara Khadjeh and Vanessa Hindmarsh and Frederike Weber and Lukas Cyganek and Vidal, {Ramon O} and Setare Torkieh and Katrin Streckfuss-B{\"o}meke and Dawid Lbik and Malte Tiburcy and Mohamed, {Belal A} and Stefan Bonn and Karl Toischer and Gerd Hasenfuss",
year = "2020",
month = mar,
day = "7",
doi = "10.1007/s00395-020-0784-4",
language = "English",
volume = "115",
pages = "27",
journal = "BASIC RES CARDIOL",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "3",

}

RIS

TY - JOUR

T1 - CRISPLD1: a novel conserved target in the transition to human heart failure

AU - Khadjeh, Sara

AU - Hindmarsh, Vanessa

AU - Weber, Frederike

AU - Cyganek, Lukas

AU - Vidal, Ramon O

AU - Torkieh, Setare

AU - Streckfuss-Bömeke, Katrin

AU - Lbik, Dawid

AU - Tiburcy, Malte

AU - Mohamed, Belal A

AU - Bonn, Stefan

AU - Toischer, Karl

AU - Hasenfuss, Gerd

PY - 2020/3/7

Y1 - 2020/3/7

N2 - Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca2+ regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions.

AB - Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca2+ regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions.

KW - Amino Acid Sequence

KW - Animals

KW - Aortic Valve Stenosis/complications

KW - Apoptosis

KW - Biopsy

KW - Calcium/metabolism

KW - Calcium Signaling

KW - Cell Adhesion Molecules/chemistry

KW - Conserved Sequence

KW - Down-Regulation

KW - Evolution, Molecular

KW - Female

KW - Heart Failure/complications

KW - Humans

KW - Induced Pluripotent Stem Cells/cytology

KW - Male

KW - Mice

KW - Myocardium/metabolism

KW - Myocytes, Cardiac/cytology

KW - Transcriptome

KW - Transforming Growth Factor beta/metabolism

U2 - 10.1007/s00395-020-0784-4

DO - 10.1007/s00395-020-0784-4

M3 - SCORING: Journal article

C2 - 32146539

VL - 115

SP - 27

JO - BASIC RES CARDIOL

JF - BASIC RES CARDIOL

SN - 0300-8428

IS - 3

ER -