Peripheral blood mononuclear cells from patients with systemic sclerosis spontaneously secrete increased amounts of vascular endothelial growth factor (VEGF) already in the early stage of the disease
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INTRODUCTION
Vascular injury is considered to play a key role in the pathogenesis of systemic sclerosis (scleroderma, SSc) 1, 2. Capillary loss and characteristic deformations of the remaining capillaries are present in nearly all patients with SSc from the very beginning of the disease 3, 4, 5. It has also been shown that the severity of capillary injury correlates with the severity of internal organ involvement 5, 6. Severe ischemia leads to the development of pitting scars and severe digital ulcers.
Patients
25 patients with SSc (21 female and 4 men) were investigated. Patients selected for the study fulfilled the American College of Rheumatology (ACR) classification criteria for SSc.[19] or they had Raynaud's phenomenon and at least one of the following: microangiopathy typical for SSc in capillaroscopy, and/or autoantibodies typical for SSc, which is consistent with the definition of early SSc as proposed by LeRoy and Medsger. [20].
To avoid modification of the activity of leukocytes by
VEGF in SSc patients and healthy controls.
The total leukocyte count, differential leukocyte counts or platelet count did not differ between SSc patients and healthy controls (data not shown). PBMC from SSc patients produced significantly more VEGF (22.6 +/− 10.0 pg/mL/105 cells) compared with PBMC from healthy controls (16.7 +/− 4.0 pg/ mL/105 cells p<0.05 versus SSc patients) (Fig. 1).
The majority (19/25, 76%) of SSc patients had early disease while in the remaining 6 patients disease lasted longer than 3 years in dSSc or longer than
DISCUSSION
In the present study we found that PBMC from SSc patients spontaneously release greater amounts of VEGF as compared with PBMC from healthy subjects. To the best of our knowledge this is the first study evaluating production of VEGF by PBMC from patients with SSc. In general, our findings are consistent with previous studies showing that expression of VEGF is increased in the peripheral blood 8, 9, 10 and skin of patients with SSc 24, 25, 26. Moreover, our results indicate that PBMC might, in
CONCLUSIONS
In conclusion, we showed for the first time that PBMC form SSc patients produce higher amounts of VEGF already in the early stage of disease. Significantly higher VEGF/TWEAK ratio in SSc patients compared with healthy controls indicates that there is an imbalance in the profile of pro-angiogenic mediators produced by PBMC in SSc. Further studies should address clinical significance of our findings.
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Cited by (17)
Vascular biomarkers and correlation with peripheral vasculopathy in systemic sclerosis
2015, Autoimmunity ReviewsCitation Excerpt :Accordingly, high serum levels of VEGF did not predict new DUs [32]. Peripheral blood mononuclear cells (PBMCs) from patients with SSc were shown to produce significantly greater amounts of VEGF as compared to controls [51]. The same result was found in the group of patients without active DUs and in those with a less severe capillaroscopic pattern, when compared to controls, suggesting that SSc patients with less vascular damage produce more VEGF than controls.
A PRISMA-driven systematic review for predictive risk factors of digital ulcers in systemic sclerosis patients
2015, Autoimmunity ReviewsCitation Excerpt :In SSc patients, platelets store and transport high levels of VEGF-A, and when activated in contact with injured endothelium, may be a source of circulating VEGF-A [73]. Bielecki et al. [74] reported that peripheral blood mononuclear cells from SSc patients produce high amounts of VEGF-A in the early stage of the disease [74]. Distler et al. [71] demonstrated an increase in VEGF in SSc patients when compared to healthy controls and significantly higher levels of VEGF in dcSSc compared to lcSSc.
Increased release of soluble CD163 by the peripheral blood mononuclear cells is associated with worse prognosis in patients with systemic sclerosis
2013, Advances in Medical SciencesCitation Excerpt :The latter might be of importance in the regeneration of injured blood vessels in SSc since, as discussed above, vascular injury is common and important feature in SSc. Of note, we have previously shown that PBMC from SSc patients release significantly greater amounts of VEGF as compared with healthy controls [38]. Accordingly, injection of PBMC has been shown to improve ischemic diseases through delivery of proangiogenic mediators [39].
Impaired Angiogenesis in Systemic Sclerosis: The Emerging Role of the Antiangiogenic VEGF<inf>165</inf>b Splice Variant
2011, Trends in Cardiovascular MedicineCitation Excerpt :It could be shown that in SSc, platelets store and transport high levels of VEGF-A and, therefore, they may be a source of circulating VEGF-A in the course of SSc because of their activation at the contact of the injured endothelium (Solanilla et al. 2009). Finally, peripheral blood mononuclear cells from SSc patients were found to produce high amounts of VEGF-A in the early stage of the disease (Bielecki et al. 2011). However, it is apparent that all these studies measured total VEGF-A levels in serum and tissue samples using tools, such as commercially available enzyme-linked immunosorbent assays, antibodies, and probes, that do not distinguish between proangiogenic and antiangiogenic VEGF-A isoforms (Manetti et al. 2011).
Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review
2023, International Journal of Molecular Sciences