CLINICAL ASSOCIATIONS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS TYPE 2 RECEPTOR IN SYSTEMIC SCLEROSIS

Objective: to investigate the levels and clinical associations of vascular endothelial growth factor (VEGF) and its type 2 receptor (VEGFR-2) in patients with systemic sclerosis (SSc).
Subjects and methods. The investigation enrolled 46 patients aged 19–77 years with SSc lasting 0.5–24 years. This group included 23 patients with limited cutaneous SSc (lSSc) and 23 with diffuse cutaneous SSc (dSSc). Forced vital capacity (FVC), lung diffusing capacity (LDC), and pulmonary arterial systolic pressure (PASP) were investigated in all the patients. An enzyme immunoassay was used to estimate serum VEGF and VEGFR-2 levels in the patients and 20 healthy individuals who constituted a control group.
Results and discussion. The levels of VEGF in the healthy individuals and SSc patients ranged from 0.20 to 264.00 and from 0.02 to 1034.20 pg/ml, respectively. The mean VEGF level in the study group was more than twice that in the control group: 212.35±253.93 and 97.74±71.46 pg/ml, respectively (p=0.032). In dSSc and lSSc, the levels of VEGF were in the range of 0.02–599.80 and 0.02–1034.20 pg/ml, respectively. The VEGF level in lSSc was significantly higher than that in dSSc and averaged 267.11±268.74 and 120.40±141.09 pg/ml, respectively (p=0.012). Nineteen (41%) patients were found to have digital ulcers during examination or in the medical history. The VEGF level in the presence of the ulcers was higher than that in their absence, but this difference was statistically insignificant. PASP was greater than the upper normal limit (30 mm Hg) in 19 (43%) patients. The level of VEGF in PASP <30 and ≥31 mm Hg was in the range of 0.02–363.60 and 0.20–1034.20 pg/ml, respectively. That in elevated PASP was significantly higher than that in normal PASP (p=0.0042). The mean VEGF level in patients with LDC <50% was substantially higher than in those with LDC ≥50% (364.20±381.95 and 128.55±142.70 pg/ml, respectively; p=0.034). FVC <80% of the due value was observed in 11 (26%) of 43 patients. The level of VEGF in these patients was higher than in those with normal FVC, but this difference is statistically insignificant. In SSc patients, the level VEGFR-2 was in the range of 915.7–23 290.0 pg/ml (mean value, 5784.6±4773.8 pg/ml) and much higher than that in the control group (1552.6±272.8 pg/ml) (p<0.0001). There were no differences in the level of VEGFR-2 in the presence and absence of digital ulcers, with normal and elevated PASP, with LDC <50 or ≥50%, and with normal and reduced FVC.Correlation analysis revealed a close direct association between the level of VEGF and PASP (r=0.40; p=0.007). There was also a tendency towards an inverse correlation of LDC with VEGF levels, which was not, however, statistically significant (r=-0.28; p=0.070).

Conclusion. The patients with SSc have been found to have higher VEGF and VEGFR-2 levels. Their close association with the clinical manifestations of SSc indicates that the VEGF/VEGFR-2 axis plays a role in the pathogenesis of the disease.

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