ArticlePloS one2014
Synergy between sphingosine 1-phosphate and lipopolysaccharide signaling promotes an inflammatory, angiogenic and osteogenic response in human aortic valve interstitial cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 28 citations in OpenAlex.
- Blocking Sphingosine 1-phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease.Journal of cellular physiology · 2026Article
- Advances in Pathophysiological Mechanisms of Degenerative Aortic Valve Disease.Cardiology research · 2025Review
- Novel Biomarkers of Bone Metabolism.Nutrients · 2024Review
- The Complex Relationship between Hypoxia Signaling, Mitochondrial Dysfunction and Inflammation in Calcific Aortic Valve Disease: Insights from the Molecular Mechanisms to Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Toll-like receptor-3 contributes to the development of aortic valve stenosis.Basic research in cardiology · 2023Article
- Lysosome Function in Cardiovascular Diseases.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Review
- Omega-3 Polyunsaturated Fatty Acids and the Resolution of Inflammation: Novel Therapeutic Opportunities for Aortic Valve Stenosis?Frontiers in cell and developmental biology · 2020Review
- Adaptive immune cells in calcific aortic valve disease.American journal of physiology. Heart and circulatory physiology · 2019Review
- Article
- Role of p38 MAPK in Atherosclerosis and Aortic Valve Sclerosis.International journal of molecular sciences · 2018Review
- Metabolomics activity screening for identifying metabolites that modulate phenotype.Nature biotechnology · 2018Article
- Sphingosine 1-phosphate activation of ERM contributes to vascular calcification.Journal of lipid research · 2018Article
- Toll-Like Receptors, Inflammation, and Calcific Aortic Valve Disease.Frontiers in physiology · 2018Review
- Specific changes in circulating cytokines and growth factors induced by exercise stress testing in asymptomatic aortic valve stenosis.PloS one · 2017Article
- Article
- Valve Interstitial Cells Act in a Pericyte Manner Promoting Angiogensis and Invasion by Valve Endothelial Cells.Annals of biomedical engineering · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given that the bioactive lipid sphingosine 1-phosphate is involved in cardiovascular pathophysiology, and since lipid accumulation and inflammation are hallmarks of calcific aortic stenosis, the role of sphingosine 1-phosphate on the pro-inflammatory/pro-osteogenic pathways in human interstitial cells from aortic and pulmonary valves was investigated. Real-time PCR showed sphingosine 1-phosphate receptor expression in aortic valve interstitial cells. Exposure of cells to sphingosine 1-phosphate induced pro-inflammatory responses characterized by interleukin-6, interleukin-8, and cyclooxygenase-2 up-regulations, as observed by ELISA and Western blot. Strikingly, cell treatment with sphingosine 1-phosphate plus lipopolysaccharide resulted in the synergistic induction of cyclooxygenase-2, and intercellular adhesion molecule 1, as well as the secretion of prostaglandin E2, the soluble form of the intercellular adhesion molecule 1, and the pro-angiogenic factor vascular endothelial growth factor-A. Remarkably, the synergistic effect was significantly higher in aortic valve interstitial cells from stenotic than control valves, and was drastically lower in cells from pulmonary valves, which rarely undergo stenosis. siRNA and pharmacological analysis revealed the involvement of sphingosine 1-phosphate receptors 1/3 and Toll-like receptor-4, and downstream signaling through p38/MAPK, protein kinase C, and NF-κB. As regards pro-osteogenic pathways, sphingosine 1-phosphate induced calcium deposition and the expression of the calcification markers bone morphogenetic protein-2 and alkaline phosphatase, and enhanced the effect of lipopolysaccharide, an effect that was partially blocked by inhibition of sphingosine 1-phosphate receptors 3/2 signaling. In conclusion, the interplay between sphingosine 1-phosphate receptors and Toll-like receptor 4 signaling leads to a cooperative up-regulation of inflammatory, angiogenic, and osteogenic pathways in aortic valve interstitial cells that seems relevant to the pathogenesis of aortic stenosis and may allow the inception of new therapeutic approaches.
Indexed as
Identifiers
What OpenQuestion holds
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.