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CME Evaluation

Oral Communication Session

Vascular Biology, Blood Cells, and Immunothrombosis

Session: Lung pathology

OC 19.3 - PAR1 Inhibition Vorapaxar as a Potential Therapeutic Approach in Chronic Thromboembolic Pulmonary Hypertension: Experimental Insights and Implications

Sunday, June 23, 2024
10:00 – 10:15 ICT
Room: 208 A-D

    Presenting Author(s)

  • Lu Sun, doctoral student

    doctoral student
    Chinese Academy of Medical Sciences & Peking Union Medical College; China-Japan Friendship Hospital
    Beijing, Beijing, China (People's Republic)

    • Co-Author(s)

  • ML

    Min Liu

    postdoctor
    Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases; Peking University Health Science Center
    Beijing, Beijing, China (People's Republic)

  • Zhenguo Zhai, MD,PhD

    professor
    China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China
    Beijing, Beijing, China (People's Republic)

  • PY

    Peiran Yang

    professor
    Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences
    Beijing, Beijing, China (People's Republic)

Background: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare but severe cardiovascular disease, with one of its primary causes are incomplete dissolution of thrombi in the pulmonary arteries. In the processes of thrombus formation and dissolution, Protease-Activated Receptor 1 (PAR1) plays a crucial role, yet its specific involvement in CTEPH remains unclear.

Aims: The purpose of this study is to delve into the disease progression of CTEPH and explore potential therapeutic targets, with a specific focus on the role of PAR1in CTEPH.

Methods: We collected tissue samples from pulmonary endarterectomy (PEA) procedures in CTEPH patients and cultured primary endothelial cells from these patients and assessed the functional changes in endothelial cells stimulated by thrombin and its inhibitor vorapaxar, utilizing EdU incorporation and tube formation assays. Subsequently, we employed a murine inferior vena cava (IVC) stenosis model to simulate thrombus dissolution and orally administered vorapaxar to validate its effects on thrombus dissolution.

Results: Firstly, we observed that thrombin mediated excessive proliferation of endothelial cells (P ≤ 0.0001), disrupting their tube-forming abilities，vorapaxar significantly inhibited this process (P ≤ 0.0001). In the murine IVC model, we found that thrombus mass and volume gradually decreased over time (N = 10), consistent with thrombus dissolution. Furthermore, after administering vorapaxar for 7 days, we observed a significant reduction in thrombus mass and volume (P = 0.002, N = 10), and the vorapaxar group exhibited faster dissolution of thrombi over time compared to the control group.

Conclusion(s): In conclusion, we have found that PAR1 plays a significant role in the progression of CTEPH, and the PAR1 inhibitor vorapaxar shows potential efficacy in inhibiting thrombus dissolution, offering new prospects for CTEPH treatment.