EVALUATION OF SURROGATE MARKERS OF ENDOTHELIAL CELLS IN SYSTEMIC SCLEROSIS (SSC)

Background: SSc is characterized by endothelial cell (EC) derangement, occurring since very early stages and having a prominent role in the pathogenesis of the disease. EC, when damaged and/or activated, may release in the bloodstream a wide range of substances, represented by angiotensin converting enzyme (ACE), nitric oxide (NO), adhesion molecules, such as platelet endothelial cell adhesion molecule-1 (PECAM-1) and P-selectin, chemiokines such as Monocyte Chemoattractant Protein 1 (MCP1) and regulated upon activation and normal T cells expressed and secreted (RANTES), components of fibrinolytic system, represented by urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor 1 (PAI-1), pro- and anti-angiogenic factors, such as vascular endothelial growth factor (VEGF) and endostatin. Objectives: To evaluate the circulating levels of ACE, NO, ACE, PECAM-1, P-selectin, MCP1 and RANTES, uPA, tPA, uPAR, PAI-1, VEGF and endostatin in patients with SSc. Methods: Circulating levels of the molecules were assayed (by specific ELISA kits) in 40 SSc patients [34 lSSc, 6 dSSc, 30 women and 10 men; mean age: 55.3±15.4 years] and compared to 30 age- and sex-matched healthy controls (25 women and 5 men; mean age: 53.7±12.2 years. The levels are expressed as means ± standard deviations and compared by Student''s t-test. The differences are considered significant for p values <0.05. Results: NO levels are lower in SSc than in controls (21.34±11.vs 31.03±9.39 mM; P<0.01),VEGF is higher in SSc than in controls (20.5±8.4(21.34±11.32 vs ±14.2±3.1; P<0.05),whilst endostatin is not differerent between SSc and controls (75.5±25.4 versus 79.6±22.9).Conclusion: The low levels of NO, ACE, P-selectin and the high concentrations of PECAM-1, MCP-1 and RANTES confirm the central role of endothelial dysfunction in SSc pathogenesis. The dysregulation of fibrinolytic system components, with high levels of uPA, uPAR and tPA and low concentration of PAI-1 suggest that a dysbalance of fibrinolysis is present in SSc. These data suggest that surrogate markers of EC derangement, shown as increased or decreased in our patients, may be useful in clinical settings of SSc. However, studies on larger cohorts of patients should assess which are the most suitable and reliable EC surrogate markers to be assayed in SSc.