Background/Purpose: Histopathological hallmarks of systemic sclerosis (SSc) are perivascular infiltrates and a reduced capillary density, which precede the excessive accumulation of extracellular matrix components in the later stages of the disease. The reduced capillary density leads to a slower blood flow, to tissue ischemia. Tissue hypoxia usually initiates the formation of new blood vessels from the pre-existing microvasculature. Despite the reduced blood flow and lower oxygen pressure levels, there is no evidence for a sufficient angiogenesis in the skin of patients with SSc. Nailfold capillaroscopy (NVC) is a safe, noninvasive method for the microvascular investigation. It allows us to distinguish between primary and secondary Raynaud’s phenomenon.The aim was to assess whether blood levels of angiogenic biomarkers are associated with microvasculature changes in SSc patients.

Methods: Microvasculature changes were assessed using NVC which was performed by two independent examiners. The obtained images were analysed anonymously by two investigators blinded for the clinical and serum status of SSc patients and classified as early, active and late pattern (1). Serum or plasma levels of soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by ELISA, big endothelin-1 (BET-1) concentrations using competitive enzyme-immunoassay and von Willebrand factor antigen (vWFAg) concentrations using ELISA kit were measured. As potential disease activity markers soluble receptor of interleukin-2 (sIL-2r) and interleukin-6 (IL-6) serum levels using commercial kits were assayed. For statistical evaluation Pearson’s correlation coefficient and univariate analysis were used.

Results:

Total 40 patients (38 females) were investigated: 30 individuals with limited form, 5 with diffuse, 3 patients with sclerosis sine scleroderma, 1 with overlap syndrome and 1 with undifferentiated connective tissue disease. The mean age ± standard deviation (SD) of the whole cohort was 51±22 years and the mean disease duration ± SD was 10±7 years. 3 patients (7.5%) had early NVC pattern, 12 patients (30%) had active, 10 (58%) late pattern, and 15 (37.5%) had nonspecific changes or normal picture. The patients with late NVC pattern exhibited higher vWFAg levels than patients with active pattern (p<0.01). BET-1 and sICAM-1 serum levels were higher in the active pattern compared with late pattern (p<0.01 and p<0.05, respectively). When correlating these potential biomarkers with SSc-related clinical characteristics we found only these associations: vWFAg levels with heart arrhythmias and modified Rodnan skin score (p<0.01, p<0.05, respectively).

Conclusion: VWFAg and ET-1 increase in the late NVC pattern can be considered as an attempt to support deficient vasculogenesis. Further studies are needed to determine the role of other potential biomarkers of endothelial injury and repair in SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/correlations-between-microvasculature-changes-and-angiogenic-factors-in-systemic-sclerosis-data-from-a-single-center-registry/