Natural Signaling Molecule Could Support Safer Stroke and Heart Attack Prevention

Researchers at Heinrich Heine University Düsseldorf (HHU) and University Hospital Düsseldorf (UKD) have succeeded in identifying a new mechanism for preventing strokes, which is part of the body’s own defences. They were able to show that the messenger substance S1P can act as a biological protective shield against strokes. The researchers headed by lead author Dr Marcel Benkhoff (Department of Cardiology, Pneumology and Angiology at University Hospital Düsseldorf – UKD) have now published their findings in the renowned scientific journal Science Advances.

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.

After laboratory experiments yielded these promising results, the researchers then investigated whether the findings could be reproduced in clinical practice. A total of 74 patients with cardiovascular disease were included in the study. In these patients as well, higher S1P levels in the blood led to lower coagulation activity, suggesting a reduced risk of stroke and heart attack. 

In patient care, these study results could pave the way for a unique new therapeutic approach in the future. "We can utilize a naturally occurring mechanism that acts directly in the blood vessels, not throughout the entire body," explains lead author Marcel Benkhoff. "This means we protect against strokes and heart attacks without increasing the bleeding risk associated with conventional blood thinners." The researchers believe this could make preventive therapy possible, especially for high-risk patients for whom blood thinners are not an option due to the high risk of bleeding.

Professor Dr. Amin Polzin, corresponding author of the study, also emphasizes the potential therapeutic benefits in acute myocardial infarction. "We know from previous studies that S1P directly protects heart tissue from cell damage, even during an acute infarction," he explains. "This makes the signaling molecule an exciting approach for developing new, targeted medications."