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

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Abstract

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.

About the authors

R. T. Alekperov

V.A. Nasonova Research Institute of Rheumatology

Author for correspondence.
Email: ralekperov@list.ru
MD, PhD, Senior Research Fellow Russian Federation

E. N. Alexandrova

V.A. Nasonova Research Institute of Rheumatology

Email: fake@neicon.ru
MD, PhD, Head of Laboratory of Immunology Russian Federation

A. A. Novikov

V.A. Nasonova Research Institute of Rheumatology

Email: fake@neicon.ru
MD, PhD, Leading Research Fellow, Laboratory of Immunology Russian Federation

L. P. Ananyeva

V.A. Nasonova Research Institute of Rheumatology

Email: fake@neicon.ru
MD, PhD, Professor, Head of Laboratory of Microcirculation Russian Federation

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Copyright (c) 2018 Alekperov R.T., Alexandrova E.N., Novikov A.A., Ananyeva L.P.

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