• Eur. J. Clin. Invest. · Feb 2020

    Apold1 deficiency associates with increased arterial thrombosis in vivo.

    • Candela Diaz-Cañestro, Nicole R Bonetti, Patricia Wüst, Vanasa Nageswaran, Luca Liberale, Jürg H Beer, Fabrizio Montecucco, Thomas F Lüscher, Johannes Bohacek, and Giovanni G Camici.
    • Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.
    • Eur. J. Clin. Invest. 2020 Feb 1; 50 (2): e13191.

    BackgroundEndothelial cells regulate the formation of blood clots; thus, genes selectively expressed in these cells could primarily determine thrombus formation. Apold1 (apolipoprotein L domain containing 1) is a gene expressed by endothelial cells; whether Apold1 directly contributes to arterial thrombosis has not yet been investigated. Here, we assessed the effect of Apold1 deletion on arterial thrombus formation using an in vivo model of carotid thrombosis induced by photochemical injury.Material And MethodsApold1 knockout (Apold1-/- ) mice and wild-type (WT) littermates underwent carotid thrombosis induced by photochemical injury, and time to occlusion was recorded. Tissue factor (TF) activity and activation of mitogen-activated protein kinases (MAPKs) and phosphatidyl-inositol-3 kinase (PI3K)/Akt pathways were analysed by colorimetric assay and Western blotting in both Apold1-/- and WT mice. Finally, platelet reactivity was assessed using light transmission aggregometry.ResultsAfter photochemical injury, Apold1-/- mice exhibited shorter time to occlusion as compared to WT mice. Moreover, TF activity was increased in carotid arteries of Apold1-/- when compared to WT mice. Underlying mechanistic markers such as TF mRNA and MAPKs activation were unaffected in Apold1-/- mice. In contrast, phosphorylation of Akt was reduced in Apold1-/- as compared to WT mice. Additionally, Apold1-/- mice displayed increased platelet reactivity to stimulation with collagen compared with WT animals.ConclusionsDeficiency of Apold1 results in a prothrombotic phenotype, accompanied by increased vascular TF activity, decreased PI3K/Akt activation and increased platelet reactivity. These findings suggest Apold1 as an interesting new therapeutic target in the context of arterial thrombosis.© 2020 Stichting European Society for Clinical Investigation Journal Foundation.

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