Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity, systemic organ manifestation, and nailfold capillaroscopic abnormalities
The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE).
Materials and Methods:
Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects.
Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005).
Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE.
- Belmont H. M., Abramson S. B. and Lie J. T. (1996): Pathology and pathogenesis of vascular injury in systemic lupus erythematosus. Interaction of inflammatory cells and activated endothelium. Arthritis Rheum., 39, 9–22. CrossRef
- Bombardier C., Gladman D. D., Urowitz M. B., Caron D. and Chang C. H. and Commitee on Prognosis Studies in SLE (1992): Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum., 35, 630–640. CrossRef
- Bongard O., Bounameaux H., Miescher P. A. and De Moerloose P. (1995): Association of anticardiolipin antibodies and abnormal nailfold capillaroscopy in patients with systemic lupus erythematosus. Lupus, 4, 142–144. CrossRef
- Clancy R., Marder G., Martin V., Belmont H. M., Abramson S. B. and Buyon J. (2001): Circulating activated endothelial cells in systemic lupus erythematosus. Further evidence for diffuse vasculopathy. Arthritis Rheum., 44, 1203–1208. CrossRef
- Cronstein B. N., Reiss A. and Malhotra S. (1999): The vascular endothelium. In Kammer G. M. and Tsokos G. C. (eds.): Lupus: Molecular and cellular pathogenesis. Humana Press, Totowa, 13–20.
- Cutolo M., Sulli A., Pizzorni C. and Accardo S. (2000): Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J. Rheumatol., 27, 155–160.
- Ferrara N. (1999): Molecular and biological properties of vascular endothelial growth factor. J. Mol. Med., 77, 527–543. CrossRef
- Furtado R. N., Pucinelli M. C., Cristo V. V., Andrade L. E. and Sato E. I. (2002): Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud’s phenomenon in SLE patients. Lupus, 11, 35–41. CrossRef
- Grassi W., Del Medico P., Izzo F. and Cervini C. (2001): Microvascular involvement in systemic sclerosis: capillaroscopic findings. Semin. Arthritis Rheum., 30, 397–402. CrossRef
- Grassi W. and Del Medico P. (2004): Atlante di Capillaroscopia. Edra, Milano.
- Groen H., ter Borg E. J., Postma D. S., Wouda A. A., van der Mark T. W. and Kallenberg C. G. (1992): Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns. Am. J. Med., 93, 619–627. CrossRef
- Harada M., Mitsuyama K., Yoshida H., Sakisaka S., Taniguchi E., Kawaguchi T., Ariyoshi M., Saiki T., Sakamoto M., Nagata K., Sata M., Matsuo K. and Tanikawa K. (1998): Vascular endothelial growth factor in patients with rheumatoid arthritis. Scand. J. Rheumatol., 27, 377–380. CrossRef
- Kikuchi K., Kubo M., Kadono T., Yazawa N., Ihn H. and Tamaki K. (1998): Serum concentrations of vascular endothelial growth factor in collagen diseases. Br. J. Dermatol., 139, 1049–1051 CrossRef
- Klimiuk P. A., Sierakowski S., Latosiewicz R., Cylwik J. P., Cylwik B., Skowronski J. and Chwiecko J. (2002): Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and vascular endothelial growth factor (VEGF) in patients with distinct variants of rheumatoid synovitis. Ann. Rheum. Dis., 61, 804–809. CrossRef
- Koch A. E. (2003): Angiogenesis as a target in rheumatoid arthritis. Ann. Rheum. Dis., 62(suppl. II), ii60–ii67.
- Krishnaswamy G., Kelley J., Yerra L., Smith J. K. and Chi D. S. (1999): Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. J. Interferon Cytokine Res., 19, 91–104. CrossRef
- Kuryliszyn-Moskal A. (1998): Cytokines and soluble CD4 and CD8 molecules in rheumatoid arthritis: relationship to systemic vasculitis and microvascular capillaroscopic abnormalities. Clin. Rheumatol., 17, 489–495. CrossRef
- Kuryliszyn-Moskal A., Klimiuk P. A. and Sierakowski S. (2001): Serum autoantibodies profile and increased levels of circulating intercellular adhesion molecule-1: a reflection of the immunologically mediated systemic vasculopathy in rheumatic diseases? Arch. Immunol. Ther. Exp., 49, 423–430.
- Kuryliszyn-Moskal A., Klimiuk P. A. and Sierakowski S. (2005): Soluble adhesion molecules (sVCAM-1, sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 in patients with systemic sclerosis: relationship to organ systemic involvement. Clin. Rheumatol., 24, 111–116. CrossRef
- Lee P., Leung F. Y., Alderdice C. and Armstrong S. K. (1983): Nailfold capillary microscopy in the connective tissue diseases: a semiquantitative assessment. J. Rheumatol., 10, 930–938.
- Lee S. S., Joo Y. S., Kim W. U., Min D. J., Min J. K., Park S. H., Cho C. S. and Kim H. Y. (2001): Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin. Exp. Rheumatol., 19, 321–324.
- Navarro C., Candia-Zúńiga L., Silveira L. H., Ruiz V., Gaxiola M., Avila M. C. and Amigo M. C. (2002): Vascular endothelial growth factor plasma levels in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Lupus, 11, 21–24. CrossRef
- Paleolog E. M. (1996): Angiogenesis: a critical process in the pathogenesis of RA — a role for VEGF? Br. J. Rheumatol., 35, 917–919. CrossRef
- Pisetsky D. S. (1992): Anti-DNA antibodies in systemic lupus erythematosus. Rheum. Dis. North Am., 18, 437–454.
- Riccieri V., Spadaro A., Ceccarelli F., Scrivo R., Germano V. and Valesini G. (2005): Nailfold capillaroscopy changes in systemic lupus erythematosus: correlations with disease activity and autoantibody profile. Lupus, 14, 521–525. CrossRef
- Robak E., Sysa-Jędrzejewska A. and Robak T. (2003): Vascular endothelial growth factor and its soluble receptors VEGFR-1 and VEGFR-2 in the serum of patients with systemic lupus erythematosus. Mediators Inflamm., 12, 293–298. CrossRef
- Sundy J. S. and Haynes B. F. (1995): Pathogenic mechanisms of vessel damage in vasculitis syndromes. Rheum. Dis. Clin. North Am., 21, 861–881.
- Szekanecz Z., Szegedi G. and Koch A. E. (1998): Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance. J. Investig. Med., 46, 27–41.
- Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N. and Winchester R. J. (1982): The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum., 25, 1271–1277. CrossRef
- Vaudo G., Marchesi S., Gerli R., Allegrucci R., Giordano A., Siepi D., Pirro M., Shoenfeld Y., Schillaci G. and Mannarino E. (2004): Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann. Rheum. Dis., 63, 31–35. CrossRef
- Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity, systemic organ manifestation, and nailfold capillaroscopic abnormalities
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Archivum Immunologiae et Therapiae Experimentalis
Volume 55, Issue 3 , pp 179-185
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- systemic lupus erythematosus
- vascular endothelial growth factor
- nailfold capillaroscopy
- systemic involvement
- Industry Sectors