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Thromb Haemost 2018; 118(03): 562-571
DOI: 10.1055/s-0038-1629897
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH Stuttgart

CX3CR1/CX3CL1 Axis Mediates Platelet–Leukocyte Adhesion to Arterial Endothelium in Younger Patients with a History of Idiopathic Deep Vein Thrombosis

Elena Furio   *
,
Maria Jose García-Fuster   *
,
Josep Redon
,
Patrice Marques
,
Rebeca Ortega
,
Maria Jesus Sanz
,
Laura Piqueras
Further Information

Publication History

26 October 2017

21 December 2017

Publication Date:
12 February 2018 (online)

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Abstract

Mechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CX3CR1/CX3CL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) with a history of idiopathic DVT and without known cardiovascular risk factors and 23 aged-matched control subjects (age: 34 ± 7.8 years). Flow cytometry was used to evaluate peripheral markers of platelet activation, leukocyte immunophenotypes and CX3CR1/CX3CL1 expression in both groups. A flow chamber assay was employed to measure leukocyte arrest under dynamic conditions. Platelet activation and the percentage of circulating CX3CR1-expressing platelets, CX3CR1-expressing platelet-bound monocytes and CD8+ lymphocytes were higher in patients with DVT than in controls. Additionally, patients with DVT had increased plasma levels of CX3CL1, soluble P-selectin and platelet factor 4/CXCL4. Interestingly, this correlated with enhanced platelet–leukocyte interaction and leukocyte adhesion to TNFα-stimulated arterial endothelial cells, which was partly dependent on endothelial CX3CL1 upregulation and increased CX3CR1 expression on platelets, monocytes and lymphocytes. In conclusion, increased CX3CR1 expression on circulating platelets may constitute a prognostic marker for long-term adverse cardiovascular events in patients with DVT. Blockade of CX3CL1/CX3CR1 axis may represent a new therapeutic strategy for the prevention of cardiovascular comorbidities associated with DVT.

Keywords

deep vein thrombosis - platelets - leukocyte recruitment - chemokines - endothelial dysfunction

Authors' Contributions

L.P. and M.J.S. conceived and designed the study. E.F., M.J.G-F. and J.R. recruited and collected the information of patients. E.F., P.M. and R.O. performed the in vitro and ex vivo assays, flow cytometry and ELISA experiments. L.P. and M.J.S. wrote the manuscript. All authors reviewed the manuscript.


* Both authors contributed equally to this study.


Supplementary Material

 

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