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 and Alexandra Lucas
Affiliation: Ethel Smith Chair Vasculitis Research Section Head Vascular Research Professor of Medicine, Divisions of Cardiovascular Medicine and Rheumatology University of Florida 1600 SW Archer Rd, PO BOX 100277 Gainesville, FL, USA.
Keywords: Serpin, protease, thrombosis, thrombolysis, vascular, inflammation.
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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