The serpin solution; targeting thrombotic and thrombolytic serine proteases in inflammation

Hao Chen, Jennifer A. Davids, Donghang Zheng, Marsha Bryant, Ilze Bot, Theo J.C. van Berckel, Erik Biessen, Carl Pepine, Kate Ryman, Ann Progulski-Fox, Lakshmyya Kesavalu, Richard Moyer, Grant McFadden, Alexandra Lucas

Research output: Contribution to journalReview article

10 Scopus citations

Abstract

Serpins in the mammalian body are highly potent serine protease inhibitors which modulate both thrombotic and thrombolytic pathway activation, with direct and indirect crosstalk with immune and inflammatory pathways. In this review, we discuss mammalian and viral serpins as regulators of coagulation and inflammation. We focus first on the thrombotic and thrombolytic serine proteases and known interactions between these protease cascades and elements of the innate immune response. Serpin-mediated regulation of the thrombotic pathway is then discussed, with emphasis on those serpins that have been evaluated as potential new drugs. Finally the potential of viral serpins that target the coagulation and thrombolytic cascades as potential therapeutics for anti-inflammatory properties is discussed from basic molecular activity to studies in animal models. The studies discussed range from thrombosis and hemorrhage to vascular disease and transplant rejection and finally to sepsis and clinical studies in humans. In conclusion, these unique proteins, the serpin family, now have demonstrated therapeutic potential for a wide variety of inflammatory diseases in both animal and human studies and represent a new approach for drug development.

Original languageEnglish (US)
Pages (from-to)99-110
Number of pages12
JournalCardiovascular and Hematological Disorders - Drug Targets
Volume13
Issue number2
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Inflammation
  • Protease
  • Serpin
  • Thrombolysis
  • Thrombosis
  • Vascular

ASJC Scopus subject areas

  • Molecular Medicine
  • Hematology
  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Chen, H., Davids, J. A., Zheng, D., Bryant, M., Bot, I., van Berckel, T. J. C., Biessen, E., Pepine, C., Ryman, K., Progulski-Fox, A., Kesavalu, L., Moyer, R., McFadden, G., & Lucas, A. (2013). The serpin solution; targeting thrombotic and thrombolytic serine proteases in inflammation. Cardiovascular and Hematological Disorders - Drug Targets, 13(2), 99-110. https://doi.org/10.2174/1871529X11313020003