Abstract
To investigate whether patients with a very early diagnosis of systemic sclerosis (VEDOSS) may already present circulating markers and in vitro signs of microvascular dysfunction. Serum samples were obtained from 55 patients with systemic sclerosis (SSc), 25 patients with VEDOSS, and 55 matched healthy controls (HC). Serum levels of pan-vascular endothelial growth factor (VEGF) and soluble neuropilin-1 (sNRP-1) were measured by ELISA. Human dermal microvascular endothelial cells (H-MVEC) were cultured and stimulated with SSc, VEDOSS, and HC sera. Protein expression of NRP-1 was analyzed by Western blotting, cell proliferation by 5'-bromodeoxyuridine assay, migration capacity by wound-healing assay, and capillary-like tube formation by Matrigel assay. Serum levels of pan-VEGF were increased in patients with VEDOSS and SSc versus HC (p = 0.05 and p = 0.003, respectively). Serum levels of sNRP-1 were significantly reduced in patients with VEDOSS and SSc compared with controls (p = 0.012 and p = 0.027, respectively). NRP-1 expression was decreased in H-MVEC stimulated with VEDOSS sera (p < 0.001 vs HC). Proliferation was reduced in H-MVEC stimulated either with VEDOSS or SSc sera in comparison with HC sera (p = 0.015 and p = 0.043,...Continue Reading
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