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.
Keywords: Serpin, protease, thrombosis, thrombolysis, vascular, inflammation.
Cardiovascular & Hematological Disorders-Drug Targets
Title:The Serpin Solution; Targeting Thrombotic and Thrombolytic Serine Proteases in Inflammation
Volume: 13 Issue: 2
Author(s): 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 and Alexandra Lucas
Affiliation:
Keywords: Serpin, protease, thrombosis, thrombolysis, vascular, inflammation.
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.
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Chen Hao, Davids A. Jennifer, Zheng Donghang, Bryant Marsha, Bot Ilze, Berckel J.C. van Theo, Biessen Erik, Pepine Carl, Ryman Kate, Progulski-Fox Ann, Kesavalu Lakshmyya, Moyer Richard, McFadden Grant and Lucas Alexandra, The Serpin Solution; Targeting Thrombotic and Thrombolytic Serine Proteases in Inflammation, Cardiovascular & Hematological Disorders-Drug Targets 2013; 13 (2) . https://dx.doi.org/10.2174/1871529X11313020003
DOI https://dx.doi.org/10.2174/1871529X11313020003 |
Print ISSN 1871-529X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-4063 |
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