The earliest clinical symptoms of systemic sclerosis (SSc) relate to disturbances in the peripheral vascular system. However, detailed examination of the microcirculation including the lymphatics in the skin of patients with SSc has not been reported. The aim of our study was to examine the expression patterns of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3 and the lymphatic endothelial cell marker D2-40 in the skin of SSc patients. Skin biopsy specimens from nine patients with SSc were analysed by immunohistochemistry using antibodies against VEGFR-1, VEGFR-2, VEGFR-3 and D2-40 protein. The lumen area of lymphatic vessels was measured. The data were statistically analysed using the Mann-Whitney U test, Wilcoxon signed-ranks or Spearman's rank correlation coefficient method. The intensity of VEGFR-2 and VEGFR-3 staining in the skin of patients with SSc was significantly higher than that in healthy controls. The lumen area of lymphatic vessels in the skin of patients with SSc was significantly larger than that in healthy controls. This study details the expression of VEGFR and D2-40 in the skin of patients with SSc, and highlights a possible role of microcirculatory dysfunction in the pathogenesis of systemic sclerosis.
"Interestingly, serum VEGFR-1 level was reported to be high in patients with Crohn's disease . Increased serum VEGFR-1 in patients  seems contradictory to lack of increase in tissue level VEGFR-1 in animal studies of autoimmune diseases  , but for wound healing, we tend to believe that serum level VEGFR-1 is more likely to be increased in patients with IBD and SS which is also supported with the decreased sVEGFR levels. As a result of the decreased sVEGFR-1 level in IBD and SS, these patients will likely have excessive functions of VEGFR-1 which is characterized by relentless inflammation in these patients. "
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