ArticleThe Journal of clinical investigation2004
HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
223 citing papers in PubMed, 1 synthesis or guideline pooled it, 619 citations in OpenAlex.
- The high-density lipoprotein lipidome in metabolic syndrome: A systematic review.European journal of clinical investigation · 2026Pooled it
- Investigating the Effect of a Single Infusion of Reconstituted High-Density Lipoprotein in Patients with Symptomatic Carotid Plaques.Annals of vascular surgery · 2015Trial
- Associations Between High-Density Lipoprotein Subfraction Profiles and Heart Rate Response Following Submaximal Exercise.Biology · 2026Article
- Review
- Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology.Journal of ovarian research · 2026Review
- Mevalonic acid exerts procoagulant effect by potentiating factor Xa.Natural products and bioprospecting · 2026Article
- HDL metabolism and function in diabetes mellitus.Nature reviews. Endocrinology · 2026Review
- Predictive Value of Adiponectin for Long-Term MACEs in Non-Diabetic STEMI Patients.Journal of clinical medicine · 2025Article
- Beyond High-density Lipoprotein-cholesterol: Unraveling the Complexity of High-density Lipoprotein Functionality.Journal of atherosclerosis and thrombosis · 2025Review
- Apolipoprotein M (ApoM) Ameliorates Acute Alcohol Intoxication (AAI)-Hemorrhagic Shock and Resuscitation (HSR)-Induced Microvascular Leakage.Microcirculation (New York, N.Y. : 1994) · 2025Article
- Inhibition of sphingosine 1-phosphate receptor 3 ameliorates bleomycin-induced pulmonary fibrosis by suppressing macrophage M2 polarization.Genes & diseases · 2025Article
- Inverse relationship between circulating sphingosine-1-phosphate and precursor species and coronary artery calcification score in type 2 diabetes.Cardiovascular diabetology · 2025Observational
- Association of the Platelets to High Density Lipoprotein Cholesterol Ratio and Risk of Heart Disease Events in Middle-Aged and Elderly Chinese Population: A Retrospective Cohort Study Utilizing the CHARLS Database.Reviews in cardiovascular medicine · 2025Article
- Protective Role of High-Density Lipoprotein in Multiple Sclerosis.Antioxidants (Basel, Switzerland) · 2024Review
- Sphingolipids and Chronic Kidney Disease.Journal of clinical medicine · 2024Review
- Ying and Yang of Ceramide in the Vascular Endothelium.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Microarray analysis demonstrates up-regulation of the endothelin-1 gene with compensatory down-regulation of the ETA receptor gene in human portal vein.Bioscience reports · 2024Article
- Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and obstructive sleep apnea: a cross-sectional study from NHANES.Lipids in health and disease · 2024Article
- Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke.iScience · 2024Article
- Testosterone improved erectile function by upregulating transcriptional expression of growth factors in late androgen replacement therapy model rats.International journal of impotence research · 2024Article
163 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P3 (also known as LPB3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P3-deficient mice, Akt phosphorylation and Ca2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P3-mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.