ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The pathogenesis for atherosclerosis is still unclear, and several hypotheses have been articulated to explain the initiating events in atherogenesis. Although these hypotheses are by no means mutually exclusive, there is a growing body of recent evidence that has led to the concept that subendothelial retention of apolipoprotein B100-containing lipoproteins is the initiating event in atherogenesis. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. The present review assesses some of the studies that support this concept.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Lipoprotein-matrix interactions play an important role in arterial disease. Extracellular matrix proteoglycans bind and retain specific positively charged domains on apolipoproteins B- and E-containing lipoproteins during atherogenesis. Retained lipoproteins can undergo several modifications, which may alter their interaction with extracellular matrix molecules. Growth factors, cytokines and oxidized low density lipoproteins influence proteoglycan structure, rendering them more likely to bind and retain lipoproteins during atherogenesis. Lipoproteins, native and modified, also can modulate the expression of several of the matrix degrading enzymes present in vascular tissue, thereby influencing plaque stability. Thus, the interaction of atherogenic lipoproteins with arterial wall matrix molecules can influence the genesis and progression of atherosclerosis and its complications.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

High levels of small, dense LDL in plasma are associated with increased risk for cardiovascular disease. There are some biochemical characteristics that may render small, dense LDL particles more atherogenic than larger, buoyant LDL particles. First, small, dense LDL particles contain less phospholipids and unesterified cholesterol in their surface monolayer than do large, buoyant LDL particles. This difference in lipid content appears to induce changes in the conformation of apolipoprotein B-100, leading to more exposure of proteoglycan-binding regions. This may be one reason for the high-affinity binding of small, dense LDL to arterial proteoglycans. Reduction of the phospholipid content in the surface monolayer LDL by treatment with secretory phospholipase A2(sPLA2) forms small, dense LDL with an enhanced tendency to interact with proteoglycans. Circulating levels of sPLA2-IIA appears to be an independent risk factor for coronary artery disease and a predictor of cardiovascular events. In addition, in-vivo studies support the hypothesis that sPLA2proteins contribute to atherogenesis and its clinical consequences. These data suggest that modification of LDL by sPLA2in the arterial tissue or in plasma may be a mechanism for the generation of atherogenic lipoprotein particlesin vivo, with a high tendency to be entrapped in the arterial extracellular matrix.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Oxidation products of lipids and proteins are found in atherosclerotic plaque and in macrophage foam cells. Macrophages avidly endocytose in-vitro oxidized LDL and accumulate sterols. What is the evidence that such a process is involved in in-vivo foam cell formation? The present review surveys current knowledge on the metabolism of oxidized LDL by macrophages, and the types, amounts and location of oxidation products that accumulate in these cells. Comparable studies of lesion lipoproteins and foam cells indicate that limited extracellular lipoprotein oxidation, perhaps followed by more extensive intracellular oxidation subsequent to uptake by macrophages, is a more likely scenarioin vivo.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

CD36 has been associated with diverse normal and pathologic processes. These include scavenger receptor functions (uptake of apoptotic cells and modified lipid), lipid metabolism and fatty acid transport, adhesion, angiogenesis, modulation of inflammation, transforming growth factor-β activation, atherosclerosis, diabetes and cardiomyopathy. Although CD36 was identified more than 25 years ago, it is only with the advent of recent genetic technology thatin-vivoevidence has emerged for its physiologic and pathologic relevance. As thesein-vivostudies are expanded, we will gain further insight into the mechanism(s) by which CD36 transmits a cellular signal, and this will allow the design of specific therapeutics that impact on a particular function of CD36.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ATP-binding cassette (ABC) transporters constitute a group of evolutionary highly conserved cellular transmembrane transport proteins. Recent work has implicated ABC transporters in cellular transmembrane lipid transport and hereditary diseases have been causatively linked to defective ABC transporters translocating lipid compounds. The emerging concept that a defined subset of ABC transporters is intimately involved in cellular lipid trafficking has recently been substantiated convincingly by the finding that ABCA1 plays a central role in the regulation of HDL metabolism and macrophage targeting to the RES or the vascular wall. Differentiation dependent expression of a large number of ABC transporters in monocytes/macrophages and their regulation by sterol flux render these transporter molecules potentially critical players in atherogenesis and other chronic inflammatory diseases.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Oxidized LDL can induce an increase in intracellular calcium concentration and the activation of protein kinase C in mouse peritoneal macrophages. The activation of protein kinase C leads to the release into the culture medium of granulocyte-macrophage colony-stimulating factor, which plays a priming role in oxidized LDL-induced macrophage proliferation. The expression of granulocyte-macrophage colony-stimulating factor in macrophages by oxidized LDL is positively regulated in the 5′-flanking region of granulocyte-macrophage colony-stimulating factor gene from sequence −169 to −160, but negatively regulated from −91 to −82. Granulocyte-macrophage colony-stimulating factor released by oxidized LDL from macrophages induces proliferation in autocrine or paracrine fashion via the activation of phosphatidylinositol 3-kinase. The capacity of oxidized LDL to induce macrophage proliferationin vitromay be involved in the enhanced progression of atherosclerosisin vivo.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Dendritic cells constitute a unique family of cells able to induce primary immune responses. Over the past decade, immunologists have been increasingly preoccupied with dendritic cells and dendritic cells are now seen as a panacea for vaccine development, tumour immunotherapy and a host of other immunological applications. The recent finding of dendritic cells accumulating in atherosclerotic lesions should stimulate investigation of their contributions to atherogenesis and their potential use in anti-atherosclerosis therapies.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

A major consequence of diabetes mellitus type 2 is the accelerated development of atherosclerosis. Assessment of conventional risk factors such as plasma lipids, lipoproteins and hypertension only partly account for the excessive risk of developing cardiovascular disease in this population. Increasing evidence has emerged suggesting that conditions associated with diabetes mellitus type 2, such as insulin resistance, hyperinsulinemia and hyperglycemia, may also play a significant role in regulating ‘novel’ cardiovascular risk factors. These factors and their potential roles in the development of atherosclerosis and cardiovascular events are discussed in this review.

ISSN:0957-9672    

出版商:OVID    

年代:2000

数据来源: OVID