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: Katariina Oörni, Mia Sneck, Dieter Brömme, Markku O Pentikäinen, Ken A Lindstedt, Mikko Mäyränpää, Helena Aitio, Petri T Kovanen
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 33 Pg. 34776-84 (Aug 13 2004) ISSN: 0021-9258 [Print] United States
• PMID: 15184381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apolipoprotein B-100
• Apolipoproteins B
• Lipoproteins, LDL
• Proteoglycans
• RNA, Messenger
• Cathepsins
• Cysteine Endopeptidases
• cathepsin S
• CTSK protein, human
• Cathepsin K
• CTSF protein, human
• Cathepsin F

Topics

• Animals
• Aorta (pathology)
• Apolipoprotein B-100
• Apolipoproteins B (metabolism)
• Arteriosclerosis (metabolism)
• Blotting, Western
• Cathepsin F
• Cathepsin K
• Cathepsins (biosynthesis, metabolism)
• Cattle
• Cell-Free System
• Cells, Cultured
• Coronary Vessels (metabolism)
• Cysteine Endopeptidases (metabolism)
• Extracellular Matrix (metabolism)
• Humans
• Hydrogen-Ion Concentration
• Immunohistochemistry
• Lipoproteins, LDL (metabolism)
• Macrophages (metabolism)
• Magnetic Resonance Spectroscopy
• Microscopy, Electron
• Microscopy, Fluorescence
• Monocytes (metabolism)
• Proteoglycans (metabolism)
• RNA, Messenger (metabolism)
• Time Factors