Pharmacological relevance and potential of sphingosine 1‐phosphate in the vascular system
Bibliographic record
Abstract
Sphingosine‐1‐phosphate (S1P) was identified as a crucial molecule for regulating immune responses, inflammatory processes as well as influencing the cardiovascular system. S1P mediates differentiation, proliferation and migration during vascular development and homoeostasis. S1P is a naturally occurring lipid metabolite and is present in human blood in nanomolar concentrations. S1P is not only involved in physiological but also in pathophysiological processes. Therefore, this complex signalling system is potentially interesting for pharmacological intervention. Modulation of the system might influence inflammatory, angiogenic or vasoregulatory processes. S1P activates G‐protein coupled receptors, namely S1P1–5, whereas only S1P1–3 is present in vascular cells. S1P can also act as an intracellular signalling molecule. This review highlights the pharmacological potential of S1P signalling in the vascular system by giving an overview of S1P‐mediated processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). After a short summary of S1P metabolism and signalling pathways, the role of S1P in EC and VSMC proliferation and migration, the cause of relaxation and constriction of arterial blood vessels, the protective functions on endothelial apoptosis, as well as the regulatory function in leukocyte adhesion and inflammatory responses are summarized. This is followed by a detailed description of currently known pharmacological agonists and antagonists as new tools for mediating S1P signalling in the vasculature. The variety of effects influenced by S1P provides plenty of therapeutic targets currently under investigation for potential pharmacological intervention. LINKED ARTICLES This article is one of a set of reviews submitted to BJP in connection with talks given at the September 2010 meeting of the International Society of Hypertension in Vancouver, Canada. To view the other articles in this collection visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01167.x , http://dx.doi.org/10.1111/j.1476‐5381.2011.01235.x and http://dx.doi.org/10.1111/j.1476‐5381.2011.01366.x
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".