ArticleEuropean heart journal2023
JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study.
Article in European heart journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Pooled it
- Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- The junctional protein associated with coronary artery disease predicts adverse cardiovascular events in patients with acute coronary syndromes at high residual risk.European heart journal · 2026Observational
- Residual cardiovascular risk in coronary artery disease: from pathophysiology to established and novel therapies.Nature reviews. Cardiology · 2026Review
- Mothers against decapentaplegic homolog 4 as a proteomic hub in vascular remodeling and residual cardiovascular risk.World journal of cardiology · 2026Article
- PI3K/AKT signaling pathway: new strategies for treating atherosclerosis with plant-derived compounds.Frontiers in pharmacology · 2026Review
- Article
- Article
- Aspirin Eugenol Ester Alleviates Vascular Endothelial Ferroptosis by Enhancing Antioxidant Ability and Inhibiting the JNK/c-Jun/NCOA4/FTH Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Dexmedetomidine Reduces Chronic Stress-Related Thrombosis in a Mouse FeClFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Endothelial JCAD Worsens Acute Ischemic Stroke Outcomes by Enhancing Inflammation in Response to Ischemia/Reperfusion.JACC. Basic to translational science · 2025Article
- Endothelial JCAD: A Novel Mediator of Brain Injury in Acute Ischemic Stroke.JACC. Basic to translational science · 2025Article
- Identification of Cardiometabolic Protein Biomarkers for Acute Myocardial Infarction Using Olink Proteomics.Journal of inflammation research · 2025Article
- Dynamic profiles of 25 serum biomarkers in acute myocardial infarction.Frontiers in cardiovascular medicine · 2025Article
- MicroRNA-19a-3p inhibits endothelial dysfunction in atherosclerosis by targeting JCAD.BMC cardiovascular disorders · 2024Article
- JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis.Clinical and molecular hepatology · 2024Article
- Endothelial HRedox biology · 2024Article
- JCAD deficiency delayed liver regenerative repair through the Hippo-YAP signalling pathway.Clinical and translational medicine · 2024Article
- Nomogram model includingWorld journal of gastrointestinal surgery · 2024Article
- Combining systems pharmacology, metabolomics, and transcriptomics to reveal the mechanism of Salvia miltiorrhiza-Cortex moutan herb pair for the treatment of ischemic stroke.Frontiers in pharmacology · 2024Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
22 authors at 8 institutions in 5 countries.
Funding
Abstract
aimsVariants of the junctional cadherin 5 associated (JCAD) locus associate with acute coronary syndromes. JCAD promotes experimental atherosclerosis through the large tumor suppressor kinase 2 (LATS2)/Hippo pathway. This study investigates the role of JCAD in arterial thrombosis. METHODS AND
resultsJCAD knockout (Jcad-/-) mice underwent photochemically induced endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) treated with JCAD small interfering RNA (siJCAD), LATS2 small interfering RNA (siLATS2) or control siRNA (siSCR) were employed for in vitro assays. Plasma JCAD was measured in patients with chronic coronary syndrome or ST-elevation myocardial infarction (STEMI). Jcad-/- mice displayed reduced thrombogenicity as reflected by delayed time to carotid occlusion. Mechanisms include reduced activation of the coagulation cascade [reduced tissue factor (TF) expression and activity] and increased fibrinolysis [higher thrombus embolization episodes and D-dimer levels, reduced vascular plasminogen activator inhibitor (PAI)-1 expression]. In vitro, JCAD silencing inhibited TF and PAI-1 expression in HAECs. JCAD-silenced HAECs (siJCAD) displayed increased levels of LATS2 kinase. Yet, double JCAD and LATS2 silencing did not restore the control phenotype. si-JCAD HAECs showed increased levels of phosphoinositide 3-kinases (PI3K)/ proteinkinase B (Akt) activation, known to downregulate procoagulant expression. The PI3K/Akt pathway inhibitor-wortmannin-prevented the effect of JCAD silencing on TF and PAI-1, indicating a causative role. Also, co-immunoprecipitation unveiled a direct interaction between JCAD and Akt. Confirming in vitro findings, PI3K/Akt and P-yes-associated protein levels were higher in Jcad-/- animals. Lastly, as compared with chronic coronary syndrome, STEMI patients showed higher plasma JCAD, which notably correlated positively with both TF and PAI-1 levels.
conclusionsJCAD promotes arterial thrombosis by modulating coagulation and fibrinolysis. Herein, reported translational data suggest JCAD as a potential therapeutic target for atherothrombosis.
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