Research ExplorerPublicationsCyclic adenosine monophosphate phosphodiesterase type 4 prot...

Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias

Standard

Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. / Molina, Cristina E; Leroy, Jérôme; Richter, Wito; Xie, Moses; Scheitrum, Colleen; Lee, Illkyu-Oliver; Maack, Christoph; Rucker-Martin, Catherine; Donzeau-Gouge, Patrick; Verde, Ignacio; Llach, Anna; Hove-Madsen, Leif; Conti, Marco; Vandecasteele, Grégoire; Fischmeister, Rodolphe.

In: J AM COLL CARDIOL, Vol. 59, No. 24, 12.06.2012, p. 2182-90.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Molina, CE, Leroy, J, Richter, W, Xie, M, Scheitrum, C, Lee, I-O, Maack, C, Rucker-Martin, C, Donzeau-Gouge, P, Verde, I, Llach, A, Hove-Madsen, L, Conti, M, Vandecasteele, G & Fischmeister, R 2012, 'Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias', J AM COLL CARDIOL, vol. 59, no. 24, pp. 2182-90. https://doi.org/10.1016/j.jacc.2012.01.060

APA

Molina, C. E., Leroy, J., Richter, W., Xie, M., Scheitrum, C., Lee, I-O., Maack, C., Rucker-Martin, C., Donzeau-Gouge, P., Verde, I., Llach, A., Hove-Madsen, L., Conti, M., Vandecasteele, G., & Fischmeister, R. (2012). Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. J AM COLL CARDIOL, 59(24), 2182-90. https://doi.org/10.1016/j.jacc.2012.01.060

Vancouver

Molina CE, Leroy J, Richter W, Xie M, Scheitrum C, Lee I-O et al. Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. J AM COLL CARDIOL. 2012 Jun 12;59(24):2182-90. https://doi.org/10.1016/j.jacc.2012.01.060

Bibtex

@article{1b53452b5e184d6a861ed62421674018,
title = "Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias",
abstract = "OBJECTIVES: This study was designed to examine whether a cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to the control of electrical stability.BACKGROUND: Atrial fibrillation is accompanied by a profound remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca(2+) handling. Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting. In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic activity. However, its role in the human heart remains controversial.METHODS: L-type Ca(2+) current and spontaneous Ca(2+) release were recorded in isolated human atrial myocytes. Intracellular cAMP was measured by live cell imaging using a fluorescence resonance energy transfer-based sensor. Contractile force and arrhythmias were recorded in human atrial trabeculae. PDE activity was measured in human atrial tissue from patients in sinus rhythm and permanent atrial fibrillation.RESULTS: PDE4 is expressed in human atrial myocytes and accounts for approximately 15% of total PDE activity. PDE4D represents the major PDE4 subtype. PDE4 inhibition increased intracellular cAMP and L-type Ca(2+) current and dramatically delayed their decay after a brief β-adrenergic stimulation. PDE4 inhibition also increased the frequency of spontaneous Ca(2+) release at baseline, as well as the contractile response and the incidence of arrhythmias in human atrial strips during β-adrenergic stimulation. Total PDE activity decreased with age, and the relative PDE4 activity was lower in patients with permanent atrial fibrillation than in age-matched sinus rhythm controls.CONCLUSIONS: PDE4 is critical in controlling cAMP levels and thereby Ca(2+) influx and release in human atrial muscle, hence limiting the susceptibility to arrhythmias.",
keywords = "Arrhythmias, Cardiac, Atrial Fibrillation, Calcium, Cyclic AMP, Cyclic Nucleotide Phosphodiesterases, Type 4, Fluorescence Resonance Energy Transfer, Heart Atria, Humans, Myocytes, Cardiac, Phosphodiesterase 4 Inhibitors, Sarcoplasmic Reticulum, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Molina, {Cristina E} and J{\'e}r{\^o}me Leroy and Wito Richter and Moses Xie and Colleen Scheitrum and Illkyu-Oliver Lee and Christoph Maack and Catherine Rucker-Martin and Patrick Donzeau-Gouge and Ignacio Verde and Anna Llach and Leif Hove-Madsen and Marco Conti and Gr{\'e}goire Vandecasteele and Rodolphe Fischmeister",
note = "Copyright {\textcopyright} 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
year = "2012",
month = jun,
day = "12",
doi = "10.1016/j.jacc.2012.01.060",
language = "English",
volume = "59",
pages = "2182--90",
journal = "J AM COLL CARDIOL",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "24",

}

RIS

TY - JOUR

T1 - Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias

AU - Molina, Cristina E

AU - Leroy, Jérôme

AU - Richter, Wito

AU - Xie, Moses

AU - Scheitrum, Colleen

AU - Lee, Illkyu-Oliver

AU - Maack, Christoph

AU - Rucker-Martin, Catherine

AU - Donzeau-Gouge, Patrick

AU - Verde, Ignacio

AU - Llach, Anna

AU - Hove-Madsen, Leif

AU - Conti, Marco

AU - Vandecasteele, Grégoire

AU - Fischmeister, Rodolphe

N1 - Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2012/6/12

Y1 - 2012/6/12

N2 - OBJECTIVES: This study was designed to examine whether a cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to the control of electrical stability.BACKGROUND: Atrial fibrillation is accompanied by a profound remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca(2+) handling. Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting. In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic activity. However, its role in the human heart remains controversial.METHODS: L-type Ca(2+) current and spontaneous Ca(2+) release were recorded in isolated human atrial myocytes. Intracellular cAMP was measured by live cell imaging using a fluorescence resonance energy transfer-based sensor. Contractile force and arrhythmias were recorded in human atrial trabeculae. PDE activity was measured in human atrial tissue from patients in sinus rhythm and permanent atrial fibrillation.RESULTS: PDE4 is expressed in human atrial myocytes and accounts for approximately 15% of total PDE activity. PDE4D represents the major PDE4 subtype. PDE4 inhibition increased intracellular cAMP and L-type Ca(2+) current and dramatically delayed their decay after a brief β-adrenergic stimulation. PDE4 inhibition also increased the frequency of spontaneous Ca(2+) release at baseline, as well as the contractile response and the incidence of arrhythmias in human atrial strips during β-adrenergic stimulation. Total PDE activity decreased with age, and the relative PDE4 activity was lower in patients with permanent atrial fibrillation than in age-matched sinus rhythm controls.CONCLUSIONS: PDE4 is critical in controlling cAMP levels and thereby Ca(2+) influx and release in human atrial muscle, hence limiting the susceptibility to arrhythmias.

AB - OBJECTIVES: This study was designed to examine whether a cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to the control of electrical stability.BACKGROUND: Atrial fibrillation is accompanied by a profound remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca(2+) handling. Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting. In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic activity. However, its role in the human heart remains controversial.METHODS: L-type Ca(2+) current and spontaneous Ca(2+) release were recorded in isolated human atrial myocytes. Intracellular cAMP was measured by live cell imaging using a fluorescence resonance energy transfer-based sensor. Contractile force and arrhythmias were recorded in human atrial trabeculae. PDE activity was measured in human atrial tissue from patients in sinus rhythm and permanent atrial fibrillation.RESULTS: PDE4 is expressed in human atrial myocytes and accounts for approximately 15% of total PDE activity. PDE4D represents the major PDE4 subtype. PDE4 inhibition increased intracellular cAMP and L-type Ca(2+) current and dramatically delayed their decay after a brief β-adrenergic stimulation. PDE4 inhibition also increased the frequency of spontaneous Ca(2+) release at baseline, as well as the contractile response and the incidence of arrhythmias in human atrial strips during β-adrenergic stimulation. Total PDE activity decreased with age, and the relative PDE4 activity was lower in patients with permanent atrial fibrillation than in age-matched sinus rhythm controls.CONCLUSIONS: PDE4 is critical in controlling cAMP levels and thereby Ca(2+) influx and release in human atrial muscle, hence limiting the susceptibility to arrhythmias.

KW - Arrhythmias, Cardiac

KW - Atrial Fibrillation

KW - Calcium

KW - Cyclic AMP

KW - Cyclic Nucleotide Phosphodiesterases, Type 4

KW - Fluorescence Resonance Energy Transfer

KW - Heart Atria

KW - Humans

KW - Myocytes, Cardiac

KW - Phosphodiesterase 4 Inhibitors

KW - Sarcoplasmic Reticulum

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jacc.2012.01.060

DO - 10.1016/j.jacc.2012.01.060

M3 - SCORING: Journal article

C2 - 22676938

VL - 59

SP - 2182

EP - 2190

JO - J AM COLL CARDIOL

JF - J AM COLL CARDIOL

SN - 0735-1097

IS - 24

ER -