ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Recent findings have helped to explain the fate of cholesterol entering the arterial wall. LDL can undergo both fusion and aggregation. These changes may cause increased retention of LDL in lesion connective tissue matrix and LDL uptake by macrophages. In the cornea, apparent fusion of LDL occurs in the absence of macrophages. Mast cells may be important in LDL fusion, as mast cell-derived proteases can induce fusion of LDL through proteolysis of apolipoprotein B. LDL in arterial wall atherosclerotic lesions was found to be sialic acid-poor and ceramide-enriched. These chemical changes promote LDL aggregation. Processes that may function to remove cholesterol from the arterial wall have been reported. Macrophage-produced apolipoprotein E can mediate macrophage cholesterol efflux and macrophages can convert cholesterol to 27-oxygenated products that macrophages excrete. Alternately, another oxygenated sterol, 7-ketocholesterol, impairs macrophage cholesterol efflux. In addition, mast-cell derived chymase proteolyses HDL and reduces its capacity to stimulate cholesterol efflux.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Though sometimes regarded as merely passive, space-filling components, proteoglycans are in fact metabolically active molecules with carbohydrate and protein domains that are highly conserved throughout evolution, indicating specific, crucial functions. Here we review recent evidence that heparan sulfate proteoglycans, particularly syndecans and perlecan, are able to mediate directly the internalization of lipoproteins and other ligands, without requiring the participation of LDL receptor family members. Thus, heparan sulfate proteoglycans can function as receptors. In the case of syndecan heparan sulfate proteoglycans, efficient internalization is triggered by clustering of the transmembrane and cytoplasmic domains and then proceeds through a noncoated pit pathway, possibly caveolae. The physiologic and pathophysiologic importance of these direct heparan sulfate proteoglycan-mediated catabolic pathways in the liver and in the arterial wallin vivoremains to be settled.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Macrophage foam cells in atherosclerotic lesions accumulate free cholesterol as well as cholesteryl ester. In addition, these cells have an increased rate of phospholipid biosynthesis and accumulate intracellular phospholipid-containing membrane structures (‘whorls’). Studies with cultured macrophages have revealed the possible molecular mechanism and biological relevance of these observations. A rate-limiting enzyme of phosphatidylcholine biosynthesis, cytidine triphosphate: phosphocholine cytidylyltransferase, is post-translationally activated in response to the accumulation of free cholesterol in macrophages. This leads to an increase in phosphatidylcholine mass and the appearance of membrane whorls in these cells. We have advanced the hypothesis that this alteration in cellular phospholipid metabolism is an adaptive response to prevent the cellular free cholesterol: phospholipid ratio from reaching cytotoxic levels. Support for this hypothesis was obtained by demonstrating a direct relationship between the free cholesterol: phospholipid ratio and cellular necrosis in cultured macrophages, especially under conditions in which the phosphatidylcholine response was experimentally blunted. We propose that the eventual inability of this phospholipid response to keep up with free cholesterol accumulation in lesional macrophagesin vivomay be an important cause of macrophage necrosis and, thus, plaque progression and clinical events in advanced atherosclerotic lesions.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID