Functionally stable plasminogen activator inhibitor-1 in a family with cardiovascular disease and vitiligo
JOURNAL OF THROMBOSIS AND THROMBOLYSIS, cilt.38, sa.1, ss.50-56, 2014 (SCI-Expanded)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 38 Sayı: 1
- Basım Tarihi: 2014
- Doi Numarası: 10.1007/s11239-013-1021-x
- Dergi Adı: JOURNAL OF THROMBOSIS AND THROMBOLYSIS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.50-56
- Marmara Üniversitesi Adresli: Evet
Özet
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 +/- A 38 vs. 18.6 +/- A 6.5 ng/ml, P < 0.001) and specific activity (15.8 +/- A 10.0 vs. 7.6 +/- A 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 +/- A 0.072 vs. 0.001 +/- A 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.