2004
DOI: 10.1074/jbc.m310814200
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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 f… Show more

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Cited by 95 publications
(53 citation statements)
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“…It appears that the impact of CTSS on lipid metabolism has been elucidated only in part. In vitro cathepsins degrade apolipoprotein B in LDL, and modified LDL exhibits increased binding to proteoglycans as well as enhanced aggregation and fusion and augmented foam cell formation 15,30) . However, in our study, an increased CTSS concentration and activity at baseline correlated with a higher proportion of small, dense LDL particles in the plasma.…”
Section: Discussionmentioning
confidence: 99%
“…It appears that the impact of CTSS on lipid metabolism has been elucidated only in part. In vitro cathepsins degrade apolipoprotein B in LDL, and modified LDL exhibits increased binding to proteoglycans as well as enhanced aggregation and fusion and augmented foam cell formation 15,30) . However, in our study, an increased CTSS concentration and activity at baseline correlated with a higher proportion of small, dense LDL particles in the plasma.…”
Section: Discussionmentioning
confidence: 99%
“…CatB (4,5) and CatL (6,7) expression is enhanced in human coronary lesions, but also in human carotid lesions and abdominal aortic aneurysms (8). CatK, CatS, and CatF are also expressed in human atherosclerotic lesions (9,10), and CatB, CatD, and CatL were found in macrophage-derived foam cells in lipid-rich plaque areas (11). The pathophysiological role of Cat is underlined by the findings that deficiency of CatS and CatL in LDL receptor knock-out mice reduced atherosclerotic lesions (6,12).…”
mentioning
confidence: 99%
“…Acidic extracellular pH may increase lipoprotein modifi cation ( 71,78 ), which may in turn further decrease the extracellular pH (see below). Acidic proteases, such as cathepsins, are found extracellularly in normal and atherosclerotic intima, and they efficiently proteolyze apoB-100 leading to LDL particle fusion (79)(80)(81). Moreover, proteolysis of apoB-100 sensitizes the LDL particles to lipases, thereby promoting their lipolytic modification ( 82,83 ).…”
Section: Acidity Enhances Modification Of Apob-containing Lipoproteinsmentioning
confidence: 99%