A team from Heinrich Heine University in Düsseldorf (Germany) has described a possible new therapeutic approach that uses mechanisms of the body to prevent the formation of clots without increasing the risk of bleeding, which would reduce the probability of heart attacks and other cerebrovascular accidents.
Currently, the approach to cerebrovascular diseases relies mainly on platelet aggregation inhibitors and anticoagulants. These drugs slow down the generation of clots, but by acting directly on hemostasis, they increase the possibility of severe bleeding.
The work, published in the journal "Science Advances," proposes an alternative to this scenario. The scientists focused on two molecules produced by the body itself: sphingosine-1-phosphate (S1P) and thrombomodulin (TM).
In studies with cell cultures and mouse models, the research group found that S1P directly activates a protective mechanism in blood vessels that hinders the appearance of clots. This molecule triggers a signal in the inner layer of the vascular wall that leads to an increase in TM synthesis. In turn, TM acts as a brake against the formation of thrombi.
In mice, this pathway significantly reduced the development of arterial thrombosis and vascular occlusions, without a parallel increase in the risk of bleeding being observed.
Subsequent trials also showed that the probability of blood clots and occlusions in the vessels rises markedly when TM production falls due to a lack of S1P. This phenomenon is reversed by re-administering S1P, so that S1P acts as a kind of switch in the vasculature, reducing the risk of cerebrovascular accidents and myocardial infarctions through endogenous processes.
Validation in patients
After the results in experimental models, the researchers analyzed whether this mechanism is reflected in clinical practice. To do this, they included 74 patients with cardiovascular conditions. In this group, higher concentrations of S1P in the blood were linked to lower coagulation activity, which translates to a lower risk of suffering cerebrovascular accidents or heart attacks.
According to the authors, these findings could open the door in the future to a new therapeutic strategy in the care of patients. The principal author of the study, Marcel Benkhoff, has emphasized the relevance of being able to protect people against strokes and heart attacks without increasing the bleeding risk associated with usual anticoagulants. This option would be especially valuable for high-risk patients who cannot receive anticoagulants due to the high probability of bleeding.
Professor Amin Polzin, also a principal author, has highlighted the possible therapeutic benefits of SLP1 in the context of heart attack, demonstrated in previous works, which make this messenger molecule an "interesting starting point for the development of new specific medications."
In addition to Heinrich Heine University Düsseldorf and Düsseldorf University Hospital, the study has collaborated with the University of Vienna (Austria), the University of Oldenburg (Germany), and Imperial College London (United Kingdom).