Sphingosine kinase1: a potential therapeutic target in pulmonary arterial hypertension?

Research output: Contribution to journalComment/debate

1 Citation (Scopus)

Abstract

Sphingosine kinase1 (SphK1) knockout mice are protected against pulmonary
hypertension and expression levels of the enzyme are increased in the lungs of
pulmonary arterial hypertensive (PAH) patients. Moreover,sphingosine1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refined
strategies to target SphK1 are needed because this enzyme is protective
against endothelial dysfunction and can become resistant to SphK1 inhibitors
in vascular smooth muscle, thereby potentially limiting their effectiveness in
PAH. In addition, SphK1 is involved in maladaptive hypertrophy and we propose that heart failure might be an additional direct target for therapeutic intervention with SphK1 inhibitors.
LanguageEnglish
Pages786-798
Number of pages13
JournalTrends in Molecular Medicine
Volume23
Issue number9
Early online date5 Aug 2017
DOIs
Publication statusPublished - 30 Sep 2017

Fingerprint

Sphingosine
Pulmonary Hypertension
Therapeutics
Lung
Enzymes
Vasoconstriction
Vascular Smooth Muscle
Knockout Mice
Hypertrophy
Smooth Muscle Myocytes
Rodentia
Heart Failure
Phosphates

Keywords

  • endothelium
  • sphingosine 1-phosphate
  • sphingosine 1-phosphate receptors
  • vascular remodeling
  • vascular smooth muscle
  • vasoconstriction

Cite this

@article{4678fb0c77c7488da57ad51712c0b4c9,
title = "Sphingosine kinase1: a potential therapeutic target in pulmonary arterial hypertension?",
abstract = "Sphingosine kinase1 (SphK1) knockout mice are protected against pulmonaryhypertension and expression levels of the enzyme are increased in the lungs ofpulmonary arterial hypertensive (PAH) patients. Moreover,sphingosine1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refinedstrategies to target SphK1 are needed because this enzyme is protectiveagainst endothelial dysfunction and can become resistant to SphK1 inhibitorsin vascular smooth muscle, thereby potentially limiting their effectiveness inPAH. In addition, SphK1 is involved in maladaptive hypertrophy and we propose that heart failure might be an additional direct target for therapeutic intervention with SphK1 inhibitors.",
keywords = "endothelium, sphingosine 1-phosphate, sphingosine 1-phosphate receptors, vascular remodeling, vascular smooth muscle, vasoconstriction",
author = "Pyne, {Nigel J.} and Susan Pyne",
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doi = "10.1016/j.molmed.2017.07.001",
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journal = "Trends in Molecular Medicine",
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}

Sphingosine kinase1 : a potential therapeutic target in pulmonary arterial hypertension? / Pyne, Nigel J.; Pyne, Susan.

In: Trends in Molecular Medicine, Vol. 23, No. 9, 30.09.2017, p. 786-798.

Research output: Contribution to journalComment/debate

TY - JOUR

T1 - Sphingosine kinase1

T2 - Trends in Molecular Medicine

AU - Pyne, Nigel J.

AU - Pyne, Susan

PY - 2017/9/30

Y1 - 2017/9/30

N2 - Sphingosine kinase1 (SphK1) knockout mice are protected against pulmonaryhypertension and expression levels of the enzyme are increased in the lungs ofpulmonary arterial hypertensive (PAH) patients. Moreover,sphingosine1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refinedstrategies to target SphK1 are needed because this enzyme is protectiveagainst endothelial dysfunction and can become resistant to SphK1 inhibitorsin vascular smooth muscle, thereby potentially limiting their effectiveness inPAH. In addition, SphK1 is involved in maladaptive hypertrophy and we propose that heart failure might be an additional direct target for therapeutic intervention with SphK1 inhibitors.

AB - Sphingosine kinase1 (SphK1) knockout mice are protected against pulmonaryhypertension and expression levels of the enzyme are increased in the lungs ofpulmonary arterial hypertensive (PAH) patients. Moreover,sphingosine1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refinedstrategies to target SphK1 are needed because this enzyme is protectiveagainst endothelial dysfunction and can become resistant to SphK1 inhibitorsin vascular smooth muscle, thereby potentially limiting their effectiveness inPAH. In addition, SphK1 is involved in maladaptive hypertrophy and we propose that heart failure might be an additional direct target for therapeutic intervention with SphK1 inhibitors.

KW - endothelium

KW - sphingosine 1-phosphate

KW - sphingosine 1-phosphate receptors

KW - vascular remodeling

KW - vascular smooth muscle

KW - vasoconstriction

UR - http://www.sciencedirect.com/science/journal/14714914?sdc=1

U2 - 10.1016/j.molmed.2017.07.001

DO - 10.1016/j.molmed.2017.07.001

M3 - Comment/debate

VL - 23

SP - 786

EP - 798

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

SN - 1471-4914

IS - 9

ER -