Key result
Psychosocial stress was associated with platelet hyperreactivity, and CD37 deficiency significantly increased time to vessel occlusion in mice without altering hemostasis.
Why the study?
It was unclear how psychosocial stress accelerates thrombosis, particularly regarding platelet activation and hyperreactivity, and novel regulators such as tetraspanin CD37 remained to be identified.
Does CD37 deficiency reduce platelet hyperreactivity and thrombosis in models of psychosocial stress?
Observational (n=36)
Does CD37 deficiency reduce platelet hyperreactivity and thrombosis in models of psychosocial stress?
CD37 is identified as a novel regulator of platelet activation, suggesting it may be a therapeutic target to reduce stress-mediated thrombosis without increasing bleeding risk.
Should not yet change practice in stress-related thrombosis; leaves open CD37 as a selective antithrombotic target.
AIMS: To investigate how psychosocial stress contributes to accelerated thrombosis, focusing on platelet activation and hyperreactivity. The specific objective was to identify novel platelet regulators involved in stress-mediated thrombosis, with a particular emphasis on the tetraspanin CD37. METHODS AND RESULTS: To explore how stress contributes to platelet hyperreactivity, platelets were isolated from (i) mice that experienced chronic variable stress and stress-free controls (n = 8/group) and (ii) human subjects with self-reported high- and no-stress levels (n = 18/group), followed by RNA-sequencing. By comparing mutually expressed transcripts, a subset of genes differentially expressed following psychosocial stress was identified in both human and mouse platelets. In both mice and humans, platelet CD37 positively associates with platelet aggregation responses that underlie thrombosis, with Cd37-/- platelets exhibiting impaired integrin αIIbβ3 signalling, characterized by reduced platelet fibrinogen spreading and decreased agonist-induced αIIbβ3 activation. Consistent with a role for CD37 in regulating platelet activation responses, chimeric mice that received Cd37-/- bone marrow experienced a significantly increased time to vessel occlusion in the carotid artery FeCl3 model compared to mice reconstituted with wild-type bone marrow. CD37 deficiency did not alter haemostasis, as platelet count, coagulation metrics, prothrombin time, and partial thromboplastin time did not differ in Cd37-/- mice relative to wild-type mice. Consistent with this, bleeding time did not differ between wild-type and Cd37-/- mice following tail tip transection. CONCLUSION: This study provides new insights into the platelet-associated mechanisms underlying stress-mediated thrombosis. Identifying CD37 as a novel regulator of platelet activation responses offers potential therapeutic targets for reducing the thrombotic risk associated with psychosocial stress. The findings also contribute to understanding how psychosocial stress accelerates thrombotic events and underscore the importance of platelet activation in this process. CLINICAL TRIAL REGISTRATION: NCT02106429, NCT03022552.
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Sowa et al. (2025) conducted an observational in Psychosocial stress and thrombosis (n=36). Psychosocial stress vs. No stress was evaluated on Platelet aggregation responses and time to vessel occlusion. Psychosocial stress was associated with platelet hyperreactivity, and CD37 deficiency significantly increased time to vessel occlusion in mice without altering hemostasis.
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