EXPRESSION OF THE CYSTEINE PROTEASE LEGUMAIN IN VASCULAR AND INFLAMMATORY DISEASES

摘要

The present invention provides isolated and purified polynucleotides, polypeptides, and antibodies related to mammalian (e.g., mouse and human) legumain and the novel legumain splice variant, ZB-I. The invention further relates to the use of these isolated and purified polynucleotides, polypeptides, and antibodies, as well as other legumain and ZB-I agonists and antagonists, in modulating legumain and/or ZB-I activity, expression, and/or secretion in a cell or cell population, e.g., monocytes, macrophages, foam cells, vascular endothelial cells, kidney proximal tubule cells, arterial endothelial cells, sites of inflammatory cell invasion into a vessel intima, and neointimal lesional areas of an artery. The invention also provides legumain and ZB-I antagonists, e.g., antagonistic small molecules, antibodies and antibody fragments to legumain and ZB-I, legumain and ZB-I inhibitory polypeptides, and legumain and ZB-I inhibitory polynucleotides. The present invention is also directed to novel methods for diagnosing, prognosing, monitoring, treating, ameliorating and/or preventing vascular disorders / diseases and inflammatory disorders / diseases.