Search

Syndecan-1 is a member of the transmembrane heparan sulfate proteoglycan family, whose membrane-bound and soluble forms are involved in wound healing, inflammation and vascular biology. Because these physiological events are implicated in the pathogenesis of systemic sclerosis (SSc), we investigated the clinical association of serum syndecan-1 levels in this disease. Serum syndecan-1 levels were significantly higher in SSc patients, both in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), than in healthy individuals, while comparable between dcSSc and lcSSc groups. In late stage dcSSc patients (disease duration of >6 years), but not non-late stage dcSSc patients (≤6 years), serum syndecan-1 levels were significantly higher than in normal controls. More importantly, SSc patients with elevated serum syndecan-1 levels had higher prevalence of telangiectasia, elevated right ventricular systolic pressure and decreased diffuse capacity of the lung for carbon monoxide than those with normal levels. Therefore, soluble syndecan-1 may be related to the development of proliferative vasculopathy in SSc patients.

Heparanase is an endo-β-D-glucuronidase cleaving heparan sulfate side-chains of heparin sulfate proteoglycans, which is involved in wound healing, inflammation, neovascularization and tumor progression through the degradation and remodeling of the extracellular matrix and the release of sequestered pro-angiogenic factors. Because heparanase-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), we investigated the clinical correlation of serum heparanase levels in patients with this disease. Serum heparanase levels were significantly higher in SSc patients than in healthy individuals, while comparable between diffuse cutaneous SSc and limited cutaneous SSc subgroups. On the other hand, SSc patients with digital ulcers had serum heparanase levels significantly lower than those without. These results suggest that serum heparanase levels may be elevated in SSc patients reflecting the contribution of heparanase-dependent biological processes to the development of SSc. SSc patients with high serum heparanase levels may be protected from the development of digital ulcers due to the increased release of sequestered pro-angiogenic factors such as vascular endothelial growth factor. Therefore, serum heparanase levels may serve as a protective marker against digital ulcers in SSc patients.