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Vascular endothelial growth factor and monocyte chemoattractant protein-1 in Behçet’s patients with venous thrombosis

E. Bozoglu¹, A. Dinc², H. Erdem², S. Pay², I. Simsek², I.H. Kocar¹

¹Department of Internal Medicine and ²Division of Rheumatology, Gulhane Military School of Medicine, Ankara, Turkey.

ABSTRACT
Objective
Vascular lesions can involve both arterial and venous systems which are often the major causes complicating the disease course of Behçet’s disease (BD). Vascular endothelial growth factor (VEGF) is a stimulant of angiogenesis secondary to ischemia while monocyte chemoattractant protein 1 (MCP-1) is induced by shear stresses leading to vascular collateral development. MCP-1 has been also shown to contribute to the recanalization of venous thrombi. Tumor necrosis factor-alpha (TNF-a) is known to play a major role in the pathogenesis of BD. Furthermore, up-regulation of secreted MCP-1 and VEGF was observed following stimulation with TNF-a. In view of the above functions of VEGF, MCP-1 and TNF-a, we hypothesized that these factors may be important in the pathogenesis of thrombosis seen in BD.

Methods
A total of 36 patients with a diagnosis of BD were studied. BD patients were separated into 3 groups with respect to vascular involvement. Group BD-AT (n = 9) with acute thrombosis, BD-CT (n = 12) with chronic thrombosis and BD-MC (n = 15) with mucocutaneous involvement only. The control group (group H) was comprised of 20 healthy persons. In addition, patients with acute, DC-AT (n= 11) and patients with chronic DC-CT (n = 9) thrombosis without BD served as disease controls. Serum measurements of VEGF, MCP-1 and TNF-a were performed by quantitative sandwich ELISA. The acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured.

Results.
The levels of VEGF were significantly higher in the patients in group BD-AT than either in group BD-CT or BD-MC (p = 0.03 and p < 0.001, respectively). However, no significant difference was found for VEGF levels of thrombotic patients regarding the cause (BD-AT vs. DC-AT, p = 0.063; BD-CT vs. DC-CT, p = 0.084) or the stage of thrombosis (DC-AT vs. DC-CT, p > 0.05). Both BD patients and disease controls with acute thrombosis had significantly higher levels of MCP-1 as compared to corresponding chronic thrombosis patients (BD-AT vs. DC-CT; p < 0.001; DC-AT vs. DC-CT, p < 0.001). Patients with BD and disease controls had significantly higher serum TNF-a level when compared with healthy subjects. No significant difference with respect to serum TNF-a level was noted when patient subgroups with BD and disease controls were compared with each other. Serum levels of VEGF, MCP-1, and TNF-aa were not found to be correlated with either ESR or CRP (p > 0.05).

Conclusions
Increased levels of VEGF and MCP-1 detected in BD thrombosis suggest the possible role of those angiogenic cytokines in the pathogenesis. Although not specific for BD, detection of VEGF or MCP-1 levels seems to serve as an assay for differentiation of BD patients with acute thrombosis from chronic.

Key words
Behçet’s disease, vascular, thrombosis, venous, MCP-1, VEGF, TNF-alpha, angiogenic factors.

Ergun Bozoglu, MD, Resident in Internal Medicine; Ayhan Dinc, MD, Associate
This work was supported by Gulhane Military Medical Academy Research Center (AR-2003/36).
Please address correspondence and reprint requests: Dr. Ayhan Dinc, GATA Romatoloji BD, 06018 Etlik, Ankara, Turkey.
E-mail: adinc@gata.edu.tr