Clinical and diagnostic characteristics of peripheral vasculopathy biomarkers in systemic scleroderma

Abstract

Vascular lesion is a hallmark of systemic scleroderma (SS). Vasculopathy occurs in every patient with SS. It can be the earliest clinical manifestation or cause the main life‑threatening complications of the disease, and thus determine morbidity and mortality. In SS, progressive vascular damage is characterized by constant activation/damage and apoptosis of endothelial cells, intimal thickening and vasoconstriction, leading to the lumen obliteration. Vascular remodeling leads to a violation of their tone and a decrease in capillary blood flow, followed by tissue ischemia and chronic hypoxia. These phenomena are often accompanied by altered levels of vascular factors. Among the most significant biomarkers of vasculopathy in SS with the greatest evidence base we define anti‑AT1R and anti‑ETAR, soluble intercellular adhesion molecules (sICAM‑1), soluble molecules of adhesion of thrombocyte endothelial cells, placental growth factor (PlGF), pro‑angiogenic angiopoietin‑like protein‑3 (ANGPTL‑3), apelin, chemokines (CXCL5), galectin‑3, E‑selectin, tissue kallikrein, interleukins (IL)‑13 and ‑33, vascular endothelial growth factor (VEGF165b), matrix metalloproteinases‑12, endothelin‑1, nodal adhesion molecules which are associated with the development of either digital ulcers or changes on videocapillaroscopy typical for SS. This shows their active role in the pathogenesis of SS, especially during the disease manifestation. Data is presented on the most significant vascular biomarkers and the main connections between vascular biomarkers and capillaroscopic parameters and/or the presence of digital ulcers in SS. Vascular biomarkers can become prognostic factors of vascular damage at SS, which allows early treatment of vascular complications.