Serum Tie2 levels: Clinical association with microangiopathies in patients with systemic sclerosis

Background Tie2 and its ligand, angiopoietins (Ang), regulate the transition between vascular quiescence and angiogenesis. Although defective angiogenesis is one of the major causes of microangiopathies in systemic sclerosis (SSc), the role of Ang/Tie2 signalling in the development of SSc has never been examined. Objective To investigate the clinical significance of the soluble Tie2 domain (sTie2) in serum samples from SSc patients. Methods Serum sTie2 levels were determined by a specific enzyme-linked immunosorbent assay in 48 SSc patients and nine normal controls. Results There was no significant difference in serum sTie2 levels between SSc patients and healthy controls (14.8 ± 3.4 vs. 14.7 ± 1.1 ng/mL). When we set the cut-off value at 16.97 ng/mL (mean + 2SD) based on the data of normal controls, 27% of SSc patients showed elevated serum sTie2 levels. The frequencies of nailfold bleeding and pulmonary arterial hypertension (PAH) were significantly higher in patients with increased serum sTie2 levels than in those with sTie2 levels not elevated (70% vs. 47% and 60% vs. 21%, respectively, P < 0.05). There was also a trend towards the elevation of serum sTie2 levels in SSc patients with PAH compared to those without; however, it did not reach statistical significance (16.7 ± 3.6 vs. 14.2 ± 3.4 ng/mL, P = 0.059). Conclusion Soluble Tie2 domain (sTie2) may be related to the development of vascular abnormalities in SSc, possibly by modulating the Ang/Tie2-mediated angiogenic process. Furthermore, the serum sTie2 levels may serve as a useful marker for SSc-related PAH, contributing to early diagnosis and therapeutic intervention.