ArticlePulmonary circulation2016
Sphingosine-1-phosphate is involved in the occlusive arteriopathy of pulmonary arterial hypertension.
Article in Pulmonary circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Sphingolipid Signaling in Vascular Smooth Muscle Cells during Development and Diseases.JMA journal · 2026Review
- Sphingosine-1-phosphate induces pulmonary artery smooth muscle cell proliferation, migration and pulmonary arterial remodeling by modulating sonic hedgehog signaling effector FoxM1.Chinese medical journal · 2026Article
- Roles of Lipid Metabolism in Pulmonary Hypertension: Friend or Foe?Biomolecules · 2025Review
- The nitrofen/bisdiamine murine model of congenital diaphragmatic hernia has a pulmonary hypertension vascular phenotype consistent with human CDH.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Review
- Assessment of the Effects of Sphingosine Kinase 1/Sphingosine-1-Phosphate on Microangiogenesis at Rat Myofascial Trigger Points Using Contrast-Enhanced Ultrasonography.Journal of pain research · 2024Article
- Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension.Circulation research · 2023Article
- Using extracellular matrix derived from sugen-chronic hypoxia lung tissue to study pulmonary arterial hypertension.Frontiers in pharmacology · 2023Article
- Cross-talk between TSC2 and the extracellular matrix controls pulmonary vascular proliferation and pulmonary hypertension.Science signaling · 2022Article
- Sphingosine Kinase 1 Deficiency in Smooth Muscle Cells Protects against Hypoxia-Mediated Pulmonary Hypertension via YAP1 Signaling.International journal of molecular sciences · 2022Article
- Associations among S100A4, Sphingosine-1-Phosphate, and Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease.Oxidative medicine and cellular longevity · 2022Article
- Autoimmunity to Sphingosine-1-Phosphate-Receptors in Systemic Sclerosis and Pulmonary Arterial Hypertension.Frontiers in immunology · 2022Article
- Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine-1-Phosphate.Journal of the American Heart Association · 2021Article
- The emerging alliance of sphingosine-1-phosphate signalling and immune cells: from basic mechanisms to implications in hypertension.British journal of pharmacology · 2019Review
- Ceramide and Regulation of Vascular Tone.International journal of molecular sciences · 2019Review
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- Sphingolipids in Ventilator Induced Lung Injury: Role of Sphingosine-1-Phosphate Lyase.International journal of molecular sciences · 2018Article
- Sphingosine 1-Phosphate: A Novel Target for Lung Disorders.Frontiers in immunology · 2017Review
- Differential effects of integrin-linked kinase inhibitor Cpd22 on severe pulmonary hypertension in male and female rats.Pulmonary circulationArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH. To test this hypothesis, we used plasma samples and lung tissue from patients with idiopathic PAH (IPAH) and the Sugen5416/hypoxia/normoxia rat model of occlusive PAH. Our study revealed an increase in the plasma concentration of S1P in patients with IPAH and in early and late stages of PAH in rats. We observed increased expression of both SphK1 and SphK2 in the remodeled pulmonary arteries of patients with IPAH and PAH rats. Exogenous S1P stimulated the proliferation of cultured rat pulmonary arterial endothelial and smooth-muscle cells. We also found that 3 weeks of treatment of late-stage PAH rats with an SphK1 inhibitor reduced the increased plasma levels of S1P and the occlusive pulmonary arteriopathy. Although inhibition of SphK1 improved cardiac index and the total pulmonary artery resistance index, it did not reduce right ventricular systolic pressure or right ventricular hypertrophy. Our study supports that S1P is involved in the pathogenesis of occlusive arteriopathy in PAH and provides further evidence that S1P signaling may be a novel therapeutic target.
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