title: Functionally stable plasminogen activator inhibitor-1 in a family with cardiovascular disease and vitiligo.
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.
authors.affiliation: Department of Cardiology, Faculty of Medicine, Marmara University Hospital, Yeşilbahar Sok 68/14 Palmiye Apt., Goztepe Kadikoy, 34726, Istanbul, Turkey, agirbasli@gmail.com.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Agirbasli
authors.forename: Mesut
authors.initials: M
authors.lastname: Eren
authors.forename: Songul
authors.initials: S
authors.lastname: Yasar
authors.forename: Kenan
authors.initials: K
authors.lastname: Delil
authors.forename: Fatih
authors.initials: F
authors.lastname: Goktay
authors.forename: Ebru Toksoy
authors.initials: ET
authors.lastname: Oner
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications / Q000473:pathology; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D014820:Vitiligo / Q000097:blood* / Q000150:complications / Q000473:pathology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human