Increased expression and translocation of lysosomal cathepsins contribute to macrophage apoptosis in atherogenesis.

摘要: It has been recently reported that atherosclerotic lesions in both humans and mice express several lysosomal proteases, including cathepsins B, D, L, S, which may affect plaque development stability. The mechanisms responsible for the extralysosomal expression of related atherogenic implications remain unknown. We find lesion-dependent B L is mainly macrophage-infiltrated areas human carotid atheroma. These enzymes appear cytoplasm nuclei apoptotic macrophages (normally confined to compartment) extracellular areas. After exposure oxidized low-density lipoprotein (oxLDL) or 7beta-hydroxycholesterol (7beta-OH), initially transform into foam cells then undergo cell death. lipids induce destabilization, with leakage cytosol (cathepsins L), as detected by cytochemistry immunocytochemistry. A remarkable increase cathepsin D mRNA levels was observed after 7beta-OH exposure. Like within atheroma, intralysosomal are translocated 7beta-OH-exposed cells. Our results suggest endocytosed oxLDL oxysterols not only destabilize acidic vacuolar compartment but also cause upregulation translocation cathepsins, act cleaving during process. increased macrophage apoptosis nuclear matrix degradation atheroma play important roles rupture.