Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke?

Carina Jørgensen, Saiqa Yasmeen, Helle K Iversen, Christina Kruuse

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

Mutations in the gene encoding phosphodiesterase 4D (PDE4D) enzyme are associated with ischemic stroke; however the functional implications of such mutations are not well understood. PDE4D is part of a complex protein family modulating intracellular signalling by cyclic nucleotides. The PDE4 family includes subtypes A-D, all of which show unique intracellular, cellular and tissue distribution. PDE4D is the major subtype expressed in human atrial myocytes and involved in the pathophysiology of arrhythmias, such as atrial fibrillation. The PDE4D enzyme hydrolyses cyclic adenosine monophosphate (cAMP). Though diverging results are reported, several population based studies describe association of various PDE4D single nucleotide polymorphisms (SNP) with cardio-embolic stroke in particular. Functionally, a down regulation of PDE4D variants has been reported in stroke patients. The anti-inflammatory and vasodilator properties of PDE4 inhibitors make them suitable for treatment of stroke and cardiovascular disease. PDE4D has recently been suggested as factor in atrial fibrillation. This review summarizes the possible function of PDE4D in the brain, heart, and vasculature. Further, association of the described SNPs, in particular, with cardioembolic stroke, is reviewed. Current findings on the PDE4D mutations suggest functionality involves an increased cardiac risk factor as well as augmented risk of atrial fibrillation.

OriginalsprogEngelsk
TidsskriftJournal of the Neurological Sciences
Vol/bind359
Udgave nummer1-2
Sider (fra-til)266-74
Antal sider9
ISSN0022-510X
DOI
StatusUdgivet - 15. dec. 2015

Fingeraftryk

Mutation
Single Nucleotide Polymorphism
Type 4 Cyclic Nucleotide Phosphodiesterase
Enzymes
Down-Regulation
Population
Proteins

Citer dette

Jørgensen, Carina ; Yasmeen, Saiqa ; Iversen, Helle K ; Kruuse, Christina. / Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke?. I: Journal of the Neurological Sciences. 2015 ; Bind 359, Nr. 1-2. s. 266-74.
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title = "Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke?",
abstract = "Mutations in the gene encoding phosphodiesterase 4D (PDE4D) enzyme are associated with ischemic stroke; however the functional implications of such mutations are not well understood. PDE4D is part of a complex protein family modulating intracellular signalling by cyclic nucleotides. The PDE4 family includes subtypes A-D, all of which show unique intracellular, cellular and tissue distribution. PDE4D is the major subtype expressed in human atrial myocytes and involved in the pathophysiology of arrhythmias, such as atrial fibrillation. The PDE4D enzyme hydrolyses cyclic adenosine monophosphate (cAMP). Though diverging results are reported, several population based studies describe association of various PDE4D single nucleotide polymorphisms (SNP) with cardio-embolic stroke in particular. Functionally, a down regulation of PDE4D variants has been reported in stroke patients. The anti-inflammatory and vasodilator properties of PDE4 inhibitors make them suitable for treatment of stroke and cardiovascular disease. PDE4D has recently been suggested as factor in atrial fibrillation. This review summarizes the possible function of PDE4D in the brain, heart, and vasculature. Further, association of the described SNPs, in particular, with cardioembolic stroke, is reviewed. Current findings on the PDE4D mutations suggest functionality involves an increased cardiac risk factor as well as augmented risk of atrial fibrillation.",
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Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke? / Jørgensen, Carina; Yasmeen, Saiqa; Iversen, Helle K; Kruuse, Christina.

I: Journal of the Neurological Sciences, Bind 359, Nr. 1-2, 15.12.2015, s. 266-74.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke?

AU - Jørgensen, Carina

AU - Yasmeen, Saiqa

AU - Iversen, Helle K

AU - Kruuse, Christina

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015/12/15

Y1 - 2015/12/15

N2 - Mutations in the gene encoding phosphodiesterase 4D (PDE4D) enzyme are associated with ischemic stroke; however the functional implications of such mutations are not well understood. PDE4D is part of a complex protein family modulating intracellular signalling by cyclic nucleotides. The PDE4 family includes subtypes A-D, all of which show unique intracellular, cellular and tissue distribution. PDE4D is the major subtype expressed in human atrial myocytes and involved in the pathophysiology of arrhythmias, such as atrial fibrillation. The PDE4D enzyme hydrolyses cyclic adenosine monophosphate (cAMP). Though diverging results are reported, several population based studies describe association of various PDE4D single nucleotide polymorphisms (SNP) with cardio-embolic stroke in particular. Functionally, a down regulation of PDE4D variants has been reported in stroke patients. The anti-inflammatory and vasodilator properties of PDE4 inhibitors make them suitable for treatment of stroke and cardiovascular disease. PDE4D has recently been suggested as factor in atrial fibrillation. This review summarizes the possible function of PDE4D in the brain, heart, and vasculature. Further, association of the described SNPs, in particular, with cardioembolic stroke, is reviewed. Current findings on the PDE4D mutations suggest functionality involves an increased cardiac risk factor as well as augmented risk of atrial fibrillation.

AB - Mutations in the gene encoding phosphodiesterase 4D (PDE4D) enzyme are associated with ischemic stroke; however the functional implications of such mutations are not well understood. PDE4D is part of a complex protein family modulating intracellular signalling by cyclic nucleotides. The PDE4 family includes subtypes A-D, all of which show unique intracellular, cellular and tissue distribution. PDE4D is the major subtype expressed in human atrial myocytes and involved in the pathophysiology of arrhythmias, such as atrial fibrillation. The PDE4D enzyme hydrolyses cyclic adenosine monophosphate (cAMP). Though diverging results are reported, several population based studies describe association of various PDE4D single nucleotide polymorphisms (SNP) with cardio-embolic stroke in particular. Functionally, a down regulation of PDE4D variants has been reported in stroke patients. The anti-inflammatory and vasodilator properties of PDE4 inhibitors make them suitable for treatment of stroke and cardiovascular disease. PDE4D has recently been suggested as factor in atrial fibrillation. This review summarizes the possible function of PDE4D in the brain, heart, and vasculature. Further, association of the described SNPs, in particular, with cardioembolic stroke, is reviewed. Current findings on the PDE4D mutations suggest functionality involves an increased cardiac risk factor as well as augmented risk of atrial fibrillation.

KW - Atrial Fibrillation/genetics

KW - Cyclic Nucleotide Phosphodiesterases, Type 4/genetics

KW - Genetic Predisposition to Disease/genetics

KW - Humans

KW - Mutation/genetics

KW - Risk Factors

KW - Stroke/genetics

U2 - 10.1016/j.jns.2015.11.010

DO - 10.1016/j.jns.2015.11.010

M3 - Review

VL - 359

SP - 266

EP - 274

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 1-2

ER -