JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study
An erratum to this article was published (Eur Heart J, 21 May 2023 ↗)
Authors' conclusion
JCAD promotes arterial thrombosis by modulating coagulation and fibrinolysis.
Study context
- Population
- JCAD knockout mice with photochemically induced endothelial injury; primary human aortic endothelial cells; patients with chronic coronary syndrome or STEMI
- Comparison
- Jcad-/- vs wild-type mice; siJCAD vs siSCR human aortic endothelial cells (HAECs); STEMI vs chronic coronary syndrome patients
Methodological detailstranslational, knockout mouse model, in vitro HAECs
- Translational
- Knockout mouse model
- In vitro HAECs
Main finding
As reported in the abstract
- Jcad-/- mice: reduced thrombogenicity (delayed time to carotid occlusion)
- Jcad-/- mice: reduced tissue factor (TF) expression and activity
- Jcad-/- mice: increased fibrinolysis (more thrombus embolization episodes, higher D-dimer, reduced vascular PAI-1 expression)
- JCAD silencing inhibited TF and PAI-1 expression in HAECs
- siJCAD HAECs: increased LATS2; double JCAD and LATS2 silencing did not restore control phenotype
- siJCAD HAECs: increased PI3K/Akt activation; wortmannin prevented effect of JCAD silencing on TF and PAI-1
- Direct interaction between JCAD and Akt (co-immunoprecipitation)
- PI3K/Akt and P-yes-associated protein levels higher in Jcad-/- animals
- STEMI vs chronic coronary syndrome: higher plasma JCAD, correlating positively with TF and PAI-1
Original publication
JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study. Eur Heart J. Published 5 December 2022. doi:10.
Summarised from the published abstract; every number is checked against it