Cathepsins F and S block HDL3-induced cholesterol efflux from macrophage foam cells.
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.
Lindstedt
Leena
L
Wihuri Research Institute, Helsinki, Finland.
Lee
Miriam
M
Oörni
Katariina
K
Brömme
Dieter
D
Kovanen
Petri T
PT
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D056646:Cathepsin F; D056657:Cathepsin K; D002403:Cathepsins / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000493:pharmacokinetics*; D005260:Female; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053440:Lipoproteins, HDL3; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D002784:Cholesterol; D002403:Cathepsins; C028217:cathepsin S; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D056646:Cathepsin F; C534092:Ctsf protein, mouse