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.
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.
Distler
Oliver
O
Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Switzerland.
Del Rosso
Angela
A
Giacomelli
Roberto
R
Cipriani
Paola
P
Conforti
Maria L
ML
Guiducci
Serena
S
Gay
Renate E
RE
Michel
Beat A
BA
Brühlmann
Pius
P
Müller-Ladner
Ulf
U
Gay
Steffen
S
Matucci-Cerinic
Marco
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D002196:Capillaries / Q000254:growth & development / Q000473:pathology; D003094:Collagen / Q000097:blood*; D004264:DNA Topoisomerases, Type I; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005385:Fingers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D020678:Microscopic Angioscopy; D008875:Middle Aged; D009262:Nails / Q000098:blood supply / Q000473:pathology; D009687:Nuclear Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000097:blood*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications / Q000473:pathology; D012883:Skin Ulcer / Q000209:etiology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D001324:Autoantigens; D043169:Endostatins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009687:Nuclear Proteins; D010446:Peptide Fragments; C048100:Scl 70 antigen, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D004264:DNA Topoisomerases, Type I