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.
Subject(s)
CX3C Chemokine Receptor 1/physiology , Chemokine CX3CL1/physiology , Endothelium, Vascular/metabolism , Leukocytes/cytology , Platelet Adhesiveness , Venous Thrombosis/metabolism , Adolescent , Adult , Case-Control Studies , Comorbidity , Endothelial Cells/cytology , Female , Human Umbilical Vein Endothelial Cells , Humans , Immunophenotyping , Inflammation , Lymphocytes/metabolism , Male , Microscopy, Fluorescence , Middle Aged , Monocytes/metabolism , Platelet Activation , Risk Factors , Tumor Necrosis Factor-alpha/metabolism , Young AdultABSTRACT
BACKGROUND: Asymptomatic or silent pulmonary embolism (S-PE) in patients with deep vein thrombosis has been the focus of numerous publications with the objective of determining the incidence of S-PE and assessing whether its existence has any clinical or therapeutic consequences that outweigh the risks associated with the diagnostic tests performed and the increased healthcare costs. The objectives were to assess the incidence of S-PE using computed tomography angiogram (CTA), to understand the epidemiological factors that might trigger embolism, and to assess whether D-dimer (DD) predicts the existence of S-PE's. METHODS: A prospective and consecutive assessment of 103 hospitalized patients with lower limb DVT in the absence of PE symptoms, using CT scan. DD was quantified before anticoagulation. The risk factors and characteristics of the DVT were studied. A three-year follow-up assessing risk recurrence and clinical outcome was performed. RESULTS: The incidence of S-PE was 66%. In 77% of these cases, the main and lobar pulmonary arteries were affected. Iliac and femoral DVTs most often produced S-PE. ROC curve with a DD value higher than 578 ng/ml provided good sensitivity but low specificity to identify patients with S-PE. Diagnosis entailed higher hospitalization expenses. No significant recurrence rate of thrombotic events was observed in the S-PE group during the follow-up. CONCLUSIONS: The incidence of S-PE in lower-limb DVT is high, but in the absence of symptoms, diagnosis does not appear to be necessary, as there are no short- or long-term clinical or therapeutic consequences.
