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Arthritis Res. 2002; 4(6): R11.
Published online Aug 30, 2002.
PMCID: PMC153841
Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers
Oliver Distler,1 Angela del Rosso,2 Roberto Giacomelli,3 Paola Cipriani,3 Maria L Conforti,2 Serena Guiducci,2 Renate E Gay,1 Beat A Michel,1 Pius Brühlmann,1 Ulf Müller-Ladner,4 Steffen Gay,corresponding author1 and Marco Matucci-Cerinic2
1Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Switzerland
2Department of Medicine, Section of Rheumatology, University of Florence, Italy
3Department of Internal Medicine and Public Health, University of L'Aquila, Italy
4Department of Internal Medicine I, University of Regensburg, Germany
corresponding authorCorresponding author.
Steffen Gay: Steffen.Gay/at/ruz.usz.ch
Received May 14, 2002; Revised July 30, 2002; Accepted August 6, 2002.
Abstract
To examine whether the lack of sufficient neoangiogenesis in systemic sclerosis (SSc) is caused by a decrease in angiogenic factors and/or an increase in angiostatic factors, the potent proangiogenic molecules vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, and the angiostatic factor endostatin were determined in patients with SSc and in healthy controls. Forty-three patients with established SSc and nine patients with pre-SSc were included in the study. Serum levels of VEGF, basic fibroblast growth factor and endostatin were measured by ELISA. Age-matched and sex-matched healthy volunteers were used as controls. Highly significant differences were found in serum levels of VEGF between SSc patients and healthy controls, whereas no differences could be detected for endostatin and basic fibroblast growth factor. Significantly higher levels of VEGF were detected in patients with Scl-70 autoantibodies and in patients with diffuse SSc. Patients with pre-SSc and short disease duration showed significant higher levels of VEGF than healthy controls, indicating that elevated serum levels of VEGF are a feature of the earliest disease stages. Patients without fingertip ulcers were found to have higher levels of VEGF than patients with fingertip ulcers. Levels of endostatin were associated with the presence of giant capillaries in nailfold capillaroscopy, but not with any other clinical parameter. The results show that the concentration of VEGF is already increased in the serum of SSc patients at the earliest stages of the disease. VEGF appears to be protective against ischemic manifestations when concentrations of VEGF exceed a certain threshold level.
Keywords: basic fibroblast growth factor, endostatin, fingertip ulcers, systemic sclerosis, vascular endothelial growth factor
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