Functionally stable plasminogen activator inhibitor-1 in a family with cardiovascular disease and vitiligo

Mehmet Agirbasli*, Mesut Eren, Songul Yasar, Kenan Delil, Fatih Goktay, Ebru Toksoy Oner, Douglas E. Vaughan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Vitiligo is a common skin condition with a complex pathophysiology characterized by the lack of pigmentation due to melanocyte degeneration. In this study, we investigated PAI-1 antigen (Ag) and activity levels in a 34 year old male with extensive vascular disease, alopecia areata and vitiligo. Fasting PAI-1 Ag and activity levels were measured at 9 a.m. in the subject and family members. Both PAI-1 Ag (67 ± 38 vs. 18.6 ± 6.5 ng/ml, P < 0.001) and specific activity (15.8 ± 10.0 vs. 7.6 ± 6.0 IU/pmol, P < 0.04) levels of PAI-1 were moderately elevated in subjects compared to the controls. PAI-1 kinetic studies demonstrated a markedly enhanced stability of plasma PAI-1 activity in the family members. Specific activity at 16 h was significantly higher than expected activity levels (0.078 ± 0.072 vs. 0.001 ± 0.001 IU/ng/ml, P < 0.001). While the exact mechanism of increased stability of PAI-1 activity in vitiligo is not known, it is likely due to post-translational modifications or increased binding affinity for a stabilizing cofactor. In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of vascular disease and associated melanocyte degeneration. Systemic or local treatment with PAI-1 inhibitors may offer a potential treatment alternative to the near orphan status for vitiligo drug development.

Original languageEnglish (US)
Pages (from-to)50-56
Number of pages7
JournalJournal of thrombosis and thrombolysis
Volume38
Issue number1
DOIs
StatePublished - Jul 2014

Keywords

  • Fibrinolysis
  • PAI-1 stability
  • Vitiligo

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

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