Sphingosine Kinase 1: A Potential Therapeutic Target in Pulmonary Arterial Hypertension?

Abstract:

:Sphingosine kinase 1 (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, sphingosine 1-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.

journal_name

Trends Mol Med

authors

Pyne NJ,Pyne S

doi

10.1016/j.molmed.2017.07.001

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

786-798

issue

9

eissn

1471-4914

issn

1471-499X

pii

S1471-4914(17)30108-9

journal_volume

23

pub_type

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