JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study
Luca Liberale1,2, Yustina M Puspitasari1, Stefano Ministrini1,3
1Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
European Heart Journal
|December 5, 2022
Summary
Junctional cadherin 5 associated (JCAD) promotes arterial thrombosis by affecting coagulation and fibrinolysis. This study reveals JCAD as a potential therapeutic target for atherothrombosis.
Area of Science:
- Cardiovascular Biology
- Thrombosis Research
- Molecular Medicine
Background:
- Junctional cadherin 5 associated (JCAD) variants are linked to acute coronary syndromes.
- JCAD influences experimental atherosclerosis via the LATS2/Hippo pathway.
Purpose of the Study:
- To investigate the role of JCAD in arterial thrombosis.
- To explore the molecular mechanisms underlying JCAD's pro-thrombotic effects.
Main Methods:
- Utilized JCAD knockout mice and primary human aortic endothelial cells (HAECs) for in vitro and in vivo thrombosis models.
- Assessed coagulation and fibrinolysis markers, including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1).
- Investigated the involvement of the PI3K/Akt pathway and direct JCAD-Akt interaction.
Main Results:
- JCAD knockout mice exhibited reduced thrombogenicity with delayed carotid occlusion.
- JCAD silencing in HAECs decreased TF and PAI-1 expression, linked to PI3K/Akt pathway activation.
- Elevated plasma JCAD levels were observed in ST-elevation myocardial infarction (STEMI) patients, correlating with TF and PAI-1.
Conclusions:
- JCAD promotes arterial thrombosis by modulating coagulation and fibrinolysis pathways.
- Translational data highlight JCAD as a potential therapeutic target for atherothrombosis.
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