Venoms versus Vasculature and Hemostasis: In Search for Non-Hemorrhagic Anti- Hemostatic Venom Components

Abstract

Snake venoms target multiple essential organ systems, among them the hemostatic system and the vasculature. Both snake venom serine proteinases (SVSPs) and snake venom metalloproteinases (SVMPs) exist which cleave coagulation factors, platelet receptors and/or extracellular matrix (ECM) components. To treat vascular occlusion and ischemic diseases, cleavage of coagulation factors and platelet receptors is a treatment goal, whereas degradation of the vessel wall ECM results in unwanted and life-threatening hemorrhages. Identification of anticoagulant and antithrombotic snake venom proteinases, which are non-hemorrhagic, provides potential new pharmacological tools. While larger forms of SVMPs belonging to the P-III and P-IIsubclasses are hemorrhagic in general, some P-I-SVMPs and SVSPs offer the potential to cleave fibrinogen thereby forming easily dissolvable clots or degrading fibrin, without attacking the vascular ECM. However, it is unclear which features of the molecular structures determine whether a P-I-SVMP belongs to this medically relevant group of fibrin(ogen)olytic, nonhemorrhagic snake venom proteinases.