Tetraspanin CD37 regulates platelet hyperreactivity and thrombosis

Area of Science:

• Cardiovascular Biology
• Hematology
• Molecular Medicine

Background:

• Psychosocial stress is linked to increased thrombotic events.
• Platelet hyperreactivity is a key mechanism in stress-mediated thrombosis.
• The specific molecular regulators of stress-induced platelet activation remain largely unknown.

Purpose of the Study:

• To investigate the role of psychosocial stress in accelerating thrombosis.
• To identify novel platelet regulators involved in stress-mediated thrombosis, focusing on the tetraspanin CD37.
• To elucidate the mechanisms of stress-induced platelet activation and hyperreactivity.

Main Methods:

• Platelets were isolated from mice and human subjects exposed to chronic variable stress or high-stress levels.
• RNA-sequencing was performed on isolated platelets to identify differentially expressed genes.
• Functional assays were conducted on Cd37-/- platelets and chimeric mice to assess platelet activation, aggregation, and thrombosis.
• Hemostasis and bleeding times were evaluated in Cd37-/- mice.

Main Results:

• Psychosocial stress led to differential gene expression in human and mouse platelets.
• Platelet CD37 expression positively correlated with platelet aggregation in both species.
• Cd37-/- platelets showed impaired integrin αIIbβ3 signaling, reduced fibrinogen spreading, and decreased agonist-induced activation.
• Mice lacking CD37 exhibited a significantly increased time to vessel occlusion in a FeCl3-induced thrombosis model.
• CD37 deficiency did not affect hemostasis, coagulation parameters, or bleeding time.

Conclusions:

• CD37 is a novel regulator of platelet activation and hyperreactivity in response to psychosocial stress.
• Targeting CD37 presents a potential therapeutic strategy for mitigating thrombotic risk associated with stress.
• This study enhances understanding of the molecular mechanisms linking psychosocial stress to accelerated thrombosis.