Abstract
Tie1 is an endothelial cell-specific tyrosine kinase receptor, which maintains vascular integrity and regulates angiogenesis via modulating angiopoietin/Tie2 signaling. Since the altered angiogenesis is closely related to the developmental process of systemic sclerosis (SSc), we herein investigated the clinical significance of serum soluble Tie1 (sTie1) levels and the expression levels of Tie1 in dermal microvascular endothelial cells (DMECs) in patients with SSc. Although serum sTie1 levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and healthy controls, SSc patients with decreased serum sTie1 levels had significantly shorter disease duration than those with serum sTie1 levels not decreased. In SSc patients with disease duration of >6 years, the prevalence of clinical symptoms associated with proliferative vasculopathy, such as digital ulcers, scleroderma renal crisis, and elevated right ventricular systolic pressure, was significantly higher in patients with decreased serum sTie1 levels than in those with serum sTie1 levels not decreased. In immunohistochemistry, Tie1 expression was reduced in DMECs of SSc patients with disease duration of <3 years compared with those of healthy controls. Collectively, in SSc patients with short disease duration, decreased serum sTie1 levels may reflect the down-regulation of Tie1 in DMECs. The decrease in serum sTie1 levels may serve as a marker of proliferative vasculopathy in SSc with disease duration of >6 years.
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Acknowledgments
We thank Tamami Kaga and Yoshiko Ito for the technical help in immunohistochemistry. This work was supported by a grant for Research on Intractable Diseases from the Ministry of Health, Labor, and Welfare of Japan.
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Noda, S., Asano, Y., Aozasa, N. et al. Clinical significance of serum soluble Tie1 levels in patients with systemic sclerosis. Arch Dermatol Res 305, 325–331 (2013). https://doi.org/10.1007/s00403-012-1307-4
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DOI: https://doi.org/10.1007/s00403-012-1307-4