title: Cysteine protease cathepsin F is expressed in human atherosclerotic lesions, is secreted by cultured macrophages, and modifies low density lipoprotein particles in vitro.
abstract: During atherogenesis, low density lipoprotein (LDL) particles in the arterial intima become modified and fuse to form extracellular lipid droplets. Proteolytic modification of apolipoprotein (apo) B-100 may be one mechanism of droplet formation from LDL. Here we studied whether the newly described acid protease cathepsin F can generate LDL-derived lipid droplets in vitro. Treatment of LDL particles with human recombinant cathepsin F led to extensive degradation of apoB-100, which, as determined by rate zonal flotation, electron microscopy, and NMR spectroscopy, triggered both aggregation and fusion of the LDL particles. Two other acid cysteine proteases, cathepsins S and K, which have been shown to be present in the arterial intima, were also capable of degrading apoB-100, albeit less efficiently. Cathepsin F treatment resulted also in enhanced retention of LDL to human arterial proteoglycans in vitro. Cultured monocyte-derived macrophages were found to secrete active cathepsin F. In addition, similarly with cathepsins S and K, cathepsin F was found to be localized mainly within the macrophage-rich areas of the human coronary atherosclerotic plaques. These results suggest that proteolytic modification of LDL by cathepsin F may be one mechanism leading to the extracellular accumulation of LDL-derived lipid droplets within the proteoglycan-rich extracellular matrix of the arterial intima during atherogenesis.
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland. kati.oorni@wri.fi
authors.forename: Katariina
authors.initials: K
authors.lastname: Oörni
authors.forename: Mia
authors.initials: M
authors.lastname: Sneck
authors.forename: Dieter
authors.initials: D
authors.lastname: Brömme
authors.forename: Markku O
authors.initials: MO
authors.lastname: Pentikäinen
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Mikko
authors.initials: M
authors.lastname: Mäyränpää
authors.forename: Helena
authors.initials: H
authors.lastname: Aitio
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D015153:Blotting, Western; D056646:Cathepsin F; D056657:Cathepsin K; D002403:Cathepsins / Q000096:biosynthesis* / Q000378:metabolism; D002417:Cattle; D002474:Cell-Free System; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K; C534090:CTSF protein, human; D056646:Cathepsin F