S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression.
M, B., P, M., B, K., M, B., T, H., G, A.K., L, S., J, S., F, K., & M, H. (2026). S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression.. Science advances. https://doi.org/10.1126/sciadv.aea9826
M B, P M, B K, M B, T H, G AK, et al. S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression.. Science advances. 2026; doi: 10.1126/sciadv.aea9826
M B, P M, B K, et al. S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression.[J]. Science advances. 2026. DOI: 10.1126/sciadv.aea9826.
@article{m2026,
author = {Benkhoff M and Mourikis P and Knoop B and Barcik M and Huckenbeck T and Al-Kassis G and Schönfelder L and Seel J and Kreuz F and Hering M},
title = {S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression.},
journal = {Science advances},
year = {2026},
doi = {10.1126/sciadv.aea9826},
note = {PMID: 42490419},
}
TY - JOUR AU - Benkhoff M AU - Mourikis P AU - Knoop B AU - Barcik M AU - Huckenbeck T AU - Al-Kassis G AU - Schönfelder L AU - Seel J AU - Kreuz F AU - Hering M TI - S1P receptor 1 signaling reduces arterial thrombosis via up-regulation of endothelial thrombomodulin expression. T2 - Science advances PY - 2026 DO - 10.1126/sciadv.aea9826 AN - PMID:42490419 ER -
Sphingosine-1-phosphate (S1P) is a key mediator in the cardiovascular system with controversial effects on coagulation. We hypothesized that S1P reduces platelet adhesion and thrombus formation by up-regulating endothelial thrombomodulin (TM), an antithrombotic protein. S1P increased endothelial TM expression via S1P receptor 1 and phosphoinositide 3-kinase signaling. S1P reduced platelet adhesion on endothelial cells in flow-chamber experiments. In the absence of endothelial cells, S1P did not affect platelet activation. In mice, S1P enhanced endothelial TM expression and decreased in vivo arterial thrombus formation but did not change bleeding time. Conversely, sphingosine kinase 1-deficient mice with low S1P concentrations showed reduced endothelial TM expression and enhanced thrombus formation, reversible by TM treatment. In line with this, in an all-comer cohort of 74 patients with cardiovascular disease, higher S1P concentrations were associated with lower circulating thrombin concentrations. In conclusion, S1P inhibited thrombus formation in an endothelium- and TM-dependent manner. This might be a therapeutic target in prevention of thrombus formation without enhancing bleeding risk.