Role of Vegetation-Associated Protease Activity in Valve Destruction in Human Infective Endocarditis

摘要: Aims Infective endocarditis (IE) is characterized by septic thrombi (vegetations) attached on heart valves, consisting of microbial colonization the valvular endocardium, that may eventually lead to congestive failure or stroke subsequent systemic embolism. We hypothesized host defense activation be directly involved in tissue proteolytic aggression, addition pathogenic effects bacterial colonization. Methods and Results IE valve samples collected during surgery (n = 39) were dissected macroscopically separating vegetations (VG) surrounding damaged part from adjacent, apparently normal (N) tissue. Corresponding conditioned media prepared separately incubation culture medium. Histological analysis showed an accumulation platelets polymorphonuclear neutrophils (PMNs) at interface between VG underlying Apoptotic cells (PMNs cells) abundantly detected this area. Plasminogen activators (PA), including urokinase (uPA) (tPA) types also associated with VG. Secreted matrix metalloproteinase (MMP) 9 was increased VG, as leukocyte elastase myeloperoxidase (MPO). The presence neutrophil extracellular traps (NETs) associating MPO externalized nucleosomes, shown immunostaining Both cell-free DNA released larger amounts than N samples, suggesting PMNs within vegetation. Finally, evidence damage obtained release fragments components such fibrinogen fibronectin, well protease-sensitive receptors uPA receptor. Conclusion Our data using human valves suggest represent important source proteases originating massive recruitment plasminergic system. latter forms a potential therapeutic target minimize degradation independently induced proteases.