Cathepsins F and S block HDL3-induced cholesterol efflux from macrophage foam cells

• Published in: Biochemical and biophysical research communications Vol. 312; no. 4; pp. 1019 - 1024
• Main Authors: Lindstedt, Leena, Lee, Miriam, Oörni, Katariina, Brömme, Dieter, Kovanen, Petri T
• Format: Journal Article
• Language: English
• Published: United States 26-12-2003
• Subjects: Animals; Apolipoprotein A-I - metabolism; Cathepsin F; Cathepsin K; Cathepsins - pharmacology; Cells, Cultured; Cholesterol - pharmacokinetics; Female; Foam Cells - drug effects; Foam Cells - metabolism; Lipoproteins, HDL - metabolism; Lipoproteins, HDL3; Macrophages - drug effects; Macrophages - metabolism; Metabolic Clearance Rate - drug effects; Mice
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2003.11.020

In atherosclerosis, accumulation of cholesterol in macrophages may partially depend on its defective removal by high-density lipoproteins (HDL). We studied the proteolytic effect of cathepsins F, S, and K on HDL(3) and on lipid-free apoA-I, and its consequence on their function as inductors of cholesterol efflux from cholesterol-filled mouse peritoneal macrophages in vitro. Incubation of HDL(3) with cathepsin F or S, but not with cathepsin K, led to rapid loss of prebeta-HDL, and reduced cholesterol efflux by 50% in only 1min. Cathepsins F or K partially degraded lipid-free apoA-I and reduced its ability to induce cholesterol efflux, whereas cathepsin S totally degraded apoA-I, leading to complete loss of apoA-I cholesterol acceptor function. These results suggest that cathepsin-secreting cells induce rapid depletion of lipid-poor (prebeta-HDL) and lipid-free apoA-I and inhibit cellular cholesterol efflux, so tending to promote the formation and maintenance of foam cells in atherosclerotic lesions.