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 Medjournal_title
Trends in molecular medicineauthors
Pyne NJ,Pyne Sdoi
10.1016/j.molmed.2017.07.001subject
Has Abstractpub_date
2017-09-01 00:00:00pages
786-798issue
9eissn
1471-4914issn
1471-499Xpii
S1471-4914(17)30108-9journal_volume
23pub_type
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