Original articlePlasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in familial Mediterranean fever
Introduction
Familial Mediterranean fever (FMF) is an autosomal recessive disease, which affects primarily Turks, Armenians, Arabs and Jews [1]. FMF is characterized by self-limiting acute febrile attacks and inflammatory reactions of serosal membranes. Several non-specific immunological abnormalities and elevations in acute-phase reactant levels were observed during FMF attacks [2]. Moreover, we—along with others—have previously demonstrated evidence for ongoing subclinical inflammation, even during attack-free periods in FMF patients [3], [4], [5].
Vascular endothelial growth factor (VEGF), a member of the platelet-derived growth factor family, is a potent and specific mitogen for endothelial cells [6], [7]. VEGF was originally thought to be an endothelial cell-derived, angiogenic, autocrine factor. However, recent reports have shown that various other cell types including macrophages [8], [9] and neutrophils [10], [11] also express significant amounts of VEGF. VEGF receptors 1 and 2 (VEGFR-1 and VEGFR-2) are the two high-affinity tyrosine kinase receptors for VEGF. VEGFR-1 gene encodes two polypeptides, a soluble VEGF-binding protein (sVEGFR-1) and a full-length membrane protein (receptor form of VEGFR-1) [12]. sVEGFR-1 is a naturally occurring VEGF antagonist, and is proved to inhibit the VEGF induced proliferation and migration of endothelial cells in vitro [13], [14], [15]. sVEGFR-1 has a physiological function in pregnancy by regulating the VEGF in a negative manner by down-regulating its activity [16]. sVEGFR-1 was detected in serum and plasma samples of normal healthy donors but the biological and physiological significance of it in vivo is not yet clear [13].
Increased VEGF levels in the circulation have been reported in a number of vascular and inflammatory diseases, including systemic vasculitis and inflammatory arthritis [17], [18], [19], [20], [21], [22]. Therefore, VEGF seems to be a non-specific marker of diseases in which endothelial cell injury and/or repair occurs. On the other hand, circulating levels of sVEGFR-1 were also increased in inflammatory arthritis [21]. In this study, we assessed sVEGFR-1 levels in patients with FMF.
Section snippets
Methods
The study groups comprised 33 FMF patients in an attack-free period (mean age 30.8 years (range 16–47); males/females 10/23), and 15 patients with acute FMF attack (mean age 32.7 years (range 19–50); males/females 7/8). All of the patients had had acute febrile peritonitis attacks. Sixteen patients had experienced arthritis (33.3%), 8 patients had had pleuritis (16.7%), and one patient had had pericarditis (2.1%) before the diagnosis of FMF. One patient was complicated with amyloidosis. The
Results
Age and sex distributions in different groups were similar. The disease durations were also comparable in patients in attack-free periods and patients with acute FMF attacks (Table 2). The levels of plasma sVEGFR-1 were expressed as mean and standard deviation (SD). Plasma sVEGFR-1 levels were 3.49 ± 1.10, 3.53 ± 1.02, and 0.37 ± 0.28 ng/ml for FMF patients in an attack-free period, FMF patients with acute attack, and healthy controls, respectively (Table 2). Plasma sVEGFR-1 levels were significantly
Discussion
In this study, we demonstrated that plasma sVEGFR-1 levels increased in patients with FMF with and without acute attacks. Plasma levels of sVEGFR-1 were comparable in patients with acute FMF attack and in attack-free periods. sVEGFR-1 values were independent of colchicine use.
Recurrent and self-limiting febrile attacks of polyserositis are characteristic features of FMF. Serum concentrations of acute phase proteins and proinflammatory cytokines are elevated in FMF patients during acute attacks.
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