Cardiovascular conditions such as strokes or heart attacks are among the most common causes of death in Germany. Today, treatment and prevention are primarily based on so-called platelet aggregation inhibitors and anticoagulants – types of medication commonly referred to as blood thinners. They inhibit or prevent blood coagulation, which in turn prevents the formation of blood clots and thus also life-threatening medical emergencies such as strokes or heart attacks. However, by intervening directly in the haemostasis process, they increase the risk of dangerous bleeding.
In a study now published in the renowned scientific journal Science Advances, researchers headed by Dr Marcel Benkhoff (Department of Cardiology, Pneumology and Angiology at the UKD) have succeeded in mapping a novel therapy approach, which utilises the body’s own mechanisms. The study focused on two substances produced by the body: sphingosine-1-phosphate (S1P) and thrombomodulin (TM). In cell and mouse models, the researchers were able to prove that S1P directly activates a mechanism in blood vessels, which prevents the formation of blood clots. The messenger substance activates a signal in the inner vascular wall, which triggers increased production of TM. This TM then prevents the formation of blood clots. This significantly reduced the development of arterial thromboses and vascular occlusions in the mouse model without increasing the risk of bleeding.
Further investigations also showed that the risk of blood clots and vascular occlusions rises again significantly when TM production falls due to a lack of S1P. This effect can be reversed by administering S1P again. S1P can thus act like a switch in the blood vessels, reducing the risk of strokes and heart attacks on the basis of the body’s own processes.
Following these promising results from experiments in the laboratory, the researchers examined in the next step whether the results could also be reproduced in day-to-day clinical operations. A total of 74 patients with cardiovascular conditions were involved in the study. Here again, a higher level of S1P in the blood resulted in lower clotting activity, which implies a reduced risk of strokes or heart attacks.
These study findings could lead to a unique new therapy approach in patient care in the future. “Here, we can utilise one of the body’s own mechanisms, which affects blood vessels directly, not the entire body,” explains lead author Marcel Benkhoff. “Accordingly, we will be able to protect individuals from strokes and heart attacks without increasing the risk of bleeding associated with common blood thinners.” As the researchers explain, this could pave the way for a preventive therapy particularly for high-risk patients who cannot take blood thinners due to the high risk of bleeding.
Professor Dr Amin Polzin, corresponding author of the study, also highlights the potential therapy benefits in the case of a heart attack: “We know from earlier studies that S1P also directly protects heart tissue from cell damage in the case of an acute myocardial infarction,” he says. “This makes the messenger substance an interesting starting point for developing new, targeted medication.”
In addition to HHU and the UKD, the University of Vienna, the University of Oldenburg and Imperial College London were also involved in the study.
Science Advances
S1P-receptor 1 signaling reduces arterial thrombosis via upregulation of endothelial thrombomodulin expression
23-Jul-2026