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CME Evaluation

Oral Communication Session

Arterial Thromboembolism

Session: Novel mechanisms and therapeutic approaches in atherothrombosis

OC 64.3 - Red blood cell-derived semaphorin 7A promotes arterial thrombosis via platelet integrin αIIb

Tuesday, June 25, 2024
15:15 – 15:30 ICT
Room: Ballroom B4

    Presenting Author(s)

  • Chaojun Tang, PhD

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

    • Co-Author(s)

  • LR

    Lijie Ren

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

  • AW

    Anni Wang

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

  • CL

    Chu Liu

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

  • QL

    Qiongyu Lu

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

  • FL

    Fengchan Li

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

  • LZ

    Li Zhu

    Ren Ai Road 199#, Su Zhou, Jiang Su Province.
    Soochow University
    Su Zhou, Jiangsu, China (People's Republic)

Background: Arterial thrombosis has always been a threat to human health. Semaphorin 7A (Sema7A), an axonal guidance molecule, is highly expressed in erythrocytes and was recently shown to promote thrombo-inflammation.

Aims: The aim of this study is to investigate the role of red blood cell-derived Sema7A in arterial thrombosis and the underlying mechanism.

Methods: We established an arterial thrombus model with higher erythrocyte composition by FeCl3 injury on the d-flow stimulated mouse carotid arteries. Sema7A-/- mice or a Sema7A-blocking antibody were used to evaluate the effect of Sema7A on the time to first occlusion after carotid artery injury, and thrombus size and composition. The adhesion of erythrocytes and platelets on collagen was examined via a flow chamber system. The downstream signaling pathways were examined by immunoprecipitation, mass spectrometry, and bioinformatics analysis.

Results: We showed that Sema7A deficiency (Figure 1A and 1B) or treatment with a Sema7A blocking antibody (Figure 1Dand 1E) significantly prolonged the time to first occlusion after carotid artery injury and reduced the thrombus size. Analysis of the thrombus composition showed that Sema7A deficiency reduced the area of erythrocytes and platelets by 50.93% and 46.82% (Figure 1C), respectively, compared to WT mice. Similarly, Sema7A blocking reduced the area of erythrocytes and platelets by 67.01% and 61.99% (Figure 1F), respectively. Erythrocyte-derived Sema7A promotes adhesion of platelets and erythrocytes to collagen and thrombus formation in vitro (Figure 2A). As verified by mass spectrometry (Figure 2B and 2C) and immunoprecipitation (Figure 2D), Sema7A regulates erythrocyte-platelet interactions by binding to the platelet surface integrin αIIb, mediating the downstream focal adhesion signaling pathway.

Conclusion(s): Red blood cell-derived Sema7A binds to platelet integrin αIIb to promote thrombus formation providing potential new approaches for the prevention and treatment of arterial thrombosis.