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

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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.

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Acknowledgments

This study is funded by Scientific Research and Projects Commission of Marmara University (BAPKO SAG-B-060510-0112).

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Authors and Affiliations

  1. Department of Cardiology, Faculty of Medicine, Marmara University Hospital, Yeşilbahar Sok 68/14 Palmiye Apt., Goztepe Kadikoy, 34726, Istanbul, Turkey

    Mehmet Agirbasli

  2. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Mesut Eren & Douglas E. Vaughan

  3. Department of Bioengineering, Faculty of Engineering, Marmara University, 34722, Istanbul, Turkey

    Songul Yasar & Ebru Toksoy Oner

  4. Department of Medical Genetics, Faculty of Medicine, Marmara University Hospital, Istanbul, Turkey

    Kenan Delil

  5. Department of Dermatology, Haydarpasa Numune Hospital, Istanbul, Turkey

    Fatih Goktay

Authors
  1. Mehmet Agirbasli
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  2. Mesut Eren
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  3. Songul Yasar
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  4. Kenan Delil
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  7. Douglas E. Vaughan
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Correspondence to Mehmet Agirbasli.

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Agirbasli, M., Eren, M., Yasar, S. et al. Functionally stable plasminogen activator inhibitor-1 in a family with cardiovascular disease and vitiligo. J Thromb Thrombolysis 38, 50–56 (2014). https://doi.org/10.1007/s11239-013-1021-x

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  • DOI: https://doi.org/10.1007/s11239-013-1021-x

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