Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis

Holly Payne, Tatyana Ponomaryov, Steve Watson, Alexander Brill

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94 Citations (Scopus)
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Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Mechanisms of DVT remain incompletely understood. Platelets play a role in DVT but the impact of specific platelet receptors remains unclear. Platelet C-type lectin-like receptor 2 (CLEC-2) is known to maintain the physiological state of blood vasculature under inflammatory conditions. DVT is a thromboinflammatory disorder developing largely as sterile inflammation in the vessel wall. We hypothesized therefore that CLEC-2 might play a role in DVT. Here, using a murine DVT model of inferior vena cava (IVC) stenosis, we demonstrate that mice with general inducible deletion of CLEC-2 or platelet-specific deficiency in CLEC-2 are protected against DVT. No phenotype in the complete stasis model was observed. Transfusion of wild-type platelets into platelet-specific CLEC-2 knockout mice restored thrombosis. Deficiency in
CLEC-2 as well as inhibition of podoplanin, a ligand of CLEC-2, was associated with reduced platelet accumulation at the IVC wall after 6 h stenosis. Podoplanin was expressed in the IVC wall, where it was localized in the vicinity of the abluminal side of the endothelium. The level of podoplanin in the IVC increased after 48 h stenosis to a substantially higher extent in mice with a thrombus vs. those without a thrombus. Treatment of animals with an anti-podoplanin neutralizing antibody resulted in development of smaller thrombi. Thus, we propose a novel mechanism of DVT, whereby CLEC-2 and up-regulation of podoplanin expression in the venous wall trigger thrombus formation
Original languageEnglish
Pages (from-to)2013-2020
Number of pages8
Issue number14
Early online date19 Jan 2017
Publication statusPublished - 6 Apr 2017


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