title: The serpin solution; targeting thrombotic and thrombolytic serine proteases in 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.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Davids
authors.forename: Donghang
authors.initials: D
authors.lastname: Zheng
authors.forename: Marsha
authors.initials: M
authors.lastname: Bryant
authors.forename: Ilze
authors.initials: I
authors.lastname: Bot
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: van Berckel
authors.forename: Erik
authors.initials: E
authors.lastname: Biessen
authors.forename: Carl
authors.initials: C
authors.lastname: Pepine
authors.forename: Kate
authors.initials: K
authors.lastname: Ryman
authors.forename: Ann
authors.initials: A
authors.lastname: Progulski-Fox
authors.forename: Lakshmyya
authors.initials: L
authors.lastname: Kesavalu
authors.forename: Richard
authors.initials: R
authors.lastname: Moyer
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lucas
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D057057:Serine Proteases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015843:Serpins / Q000494:pharmacology* / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D015842:Serine Proteinase Inhibitors; D015843:Serpins; D057057:Serine Proteases