Clinical associations of vascular endothelial growth factor in patients with systemic sclerosis

Aim: To assess serum levels of vascular endothelial growth factor (VEGF) and its clinical correlates in patients with systemic sclerosis (SSc). Materials and methods: Forty six (46) patients with SSc aged from 19 to 77 years (median, 50 years), with duration of the disease from 0.5 to 24 years (median, 7 years) were recruited into the study. There were equal numbers of the patients with limited (LSSc) and diffuse (DSSc) types of the disease (23 patients in each group, or 50%). All patients underwent clinical examination, including measurement of the forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO) and pulmonary artery systolic pressure (PASP). Serum VEGF-A levels were determined by immunoenzyme assay in the patients and in 20 healthy controls. Results: VEGF levels in the healthy individuals were in the range from 0.2 to 264 pg/mL (median, 90.2). In SSc patients they varied from 0.02 to 1034.2 pg/mL (median, 147.2), with mean VEGF levels being over 2-fold higher than that in the control group (212.35 ± 253.93 and 97.74 ± 71.46 pg/mL, respectively; p = 0.032). DSSc patients had VEGF levels of 0.02 to 599.8 pg/mL (median, 93.6), whereas in LSSc they were from 0.02 to 1034.2 pg/mL (median, 162.4). Mean VEGF level in LSSc was higher than in DSSc (267.11 ± 268.74 vs 120.4 ± 141.09 pg/mL, respectively; p = 0.012). Current or past digital ulcers were found in 19 (41%) of all patients. Mean VEGF level in the patients with digital ulcers was higher than in those without ulcers; however, the difference was not statistically significant. PASP exceeded 30 mm Hg in 19 (43%) of the patients. VEGF levels in the patients with PASP of less than 30 mm Hg and ≥ 31 mm Hg were in the range of 0.02 to 363.6 pg/mL (median, 79.6) and 0.2–1034.2 pg/mL (median, 222.3), respectively. Mean VEGF level in the patients with high PASP was significantly higher than that in the patients with normal PASP (р = 0.0042). In the patients with DLCO ≥ 50% and < 50% serum VEGF levels were found to be 0.02 to 599.8 pg/mL (median, 59.75) and 0.02 to 1034.2 pg/mL (median, 195.9), respectively. Mean VEGF levels in the patients with DLCO of less than 50% was significantly higher than in the patients with DLCO of 50% and above (364.2 ± 381.95 and 128.55 ± 142.7, respectively, р = 0.034). FVC was decreased (< 80% of predicted) in 11 (26%) of 43 patients. Mean VEGF levels in the patients with low FVC was higher than in those with normal FVC, although the difference was non-significant. There was a moderate direct association between VEGF levels and PASP values (R = 0.4; p = 0.007). Also, a trend towards an inverse correlation between DLCO and VEGF levels was observed, which was however non-significant (R = -0.28; р = 0.07). Conclusion: A significant proportion of SSc patients have high serum VEGF levels. A close association with some clinical correlates indicates a pathogenetic role of VEGF in SSc. Further studies are necessary to clarify the precise contribution of VEGF into SSc pathophysiology