ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The proliferation of smooth muscle cells (SMC) is a key event in the development of arterial lesions. Basic fibroblast growth factor is important for the replication of medial SMC, but there are few data to suggest that it is necessary for the chronic replication of intimal SMC. Heparin, a known inhibitor of SMC growth, may have its effect by its interaction with basic fibroblast growth factor. Platelet-derived growth factor is weakly mitogenic to SMCin vivo, but strongly promotes the migration of SMC into the intima after injury. Platelet-derived growth factor may also play a role in angiogenesis. SMC replication can be inhibited by antisense oligonucleotides to proliferating cell nuclear antigen and toc-myb.In vivo c-mybdelivered directly to the arterial wall inhibited arterial lesion growth induced by balloon catheter injury.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Monocyte-derived macrophages and foam cells play a central role in atherogenesis. In vitro studies suggest that macrophages exhibit many functions relevant to lesion initiation, progression, and regression. Intimal foam cells function within an incompletely understood and complex network of cytokines, growth factors, and other mediators that vary in spatial and temporal distribution during lesion formation. Macrophages may modify lipoproteins to form derivatives that then modulate lesion formation. These cells also participate in local lipid metabolism within the atherosclerotic lesion by sequestering, processing, and exporting lipids. Macrophages participate in chronic immune and inflammatory aspects of plaque formation by elaborating a vast array of mediators, and by processing and presenting antigens to T-lymphocytes. The macrophage can elaborate both stimulators and inhibitors of smooth muscle cell migration and proliferation as well as regulate the elaboration of many constituents of the vascular matrix. Macrophages also express many of the enzymes involved in degrading matrix constituents. These cells may thereby play a central role in the remodeling of the extracellular matrix during smooth muscle cell migration, neovascularization, and plaque rupture. When a plaque is ruptured, macrophage-derived proteins that modulate blood coagulation and fibrinolysis participate in local clotting and contribute to lesion evolution as well as the transition from the chronic to the acute stages of atherosclerosis. The in vivo environment of the macrophage and foam cell is extremely complex, with multiple stimuli acting concomitantly. The information derived from in vitro studies of macrophage functions has yielded hypotheses that can now be tested in vivo using increasingly powerful experimental strategies.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The endothelium overlies the developing atherosclerotic lesion and we have hypothesized that the endothelial cell (EC) may actively participate in the disease process. In response to stimuli that remain to be rigorously defined, EC may suppress functions that are important for vessel wall homeostasis and induce functions that initiate and maintain atherosclerotic plaque formation. These pro-atherogenic functions of activated or injured EC are discussed, as well as current knowledge about the initiating factors responsible for EC dysfunction, and the potential of the activated EC as a therapeutic target.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Oxidized LDL have been shown to both stimulate and inhibit functions of vascular wall cells, contributing to all stages of the atherosclerotic reaction. It is becoming clear that the family of oxidation products in LDL, like the cytokine family, has many members with varying effects on different cell types. Identification of the products of oxidized LDL that contribute to the pathogenesis of atherosclerosis will have a considerable impact on future strategies for identification of indices of clinical assessment, for prevention, and for the treatment of coronary heart disease.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Peroxidation of LDL is thought to be important in the pathogenesis of atherosclerosis, but the mechanism by which peroxidation is initiated is uncertain. Hydroxyl radical is an initiating species formed by the reaction of transition metal ions with hydrogen peroxide and of superoxide radical with nitric oxide. However, the role of the nitric oxide radical in macrophage-mediated LDL oxidation is still uncertain. In most in vitro experiments, reactions involving preformed peroxides in the LDL are being examined rather than first-chain initiation. Superoxide and transition metal ions (which are present in advanced human arteriosclerotic lesions) can lead to peroxide decomposition and propagate LDL peroxidation. The 'seeding' peroxides in LDL could be generated by lipoxygenases (other than 5-lipoxygenase), originate from dietary fats, or be formed by endogenous peroxidation, but the possibility of artefactual formation of peroxides during prolonged LDL isolation procedures must not be disregarded.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Pericellular and extracellular proteoglycans of the arterial intima interact with basic sequences of matrix proteins, lipoproteins, cytokines and enzymes. These associations appear to control the transit and function of the macromolecules in the intima. Alterations in these processes can cause focal deposition in the intima of modified apolipoprotein B-lipoproteins. Products of modified LDL appear to be atherogenic. In addition, imbalance in the function of cytokines that also interact with proteoglycans may contribute to the proliferative phase of atherogenesis and to the accumulation of foam cells.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

HDL appear to exert protective effects on the arterial wall. Research has focused on several aspects of HDL. The interaction of HDL and its subclasses with cells and cell membranes, reverse cholesterol transport, and the signal transduction cascades evoked by HDL are under intensive investigation. This has already revealed important cellular mechanisms and improved the understanding of the vasoprotective effects of HDL. HDL and several proteins carried in specific HDL subclasses (for example, clusterin, apolipoprotein H, lipoprotein-associated coagulation inhibitor) have been shown to modulate the immune system, complement system, and the clotting system. These studies will possibly help to further define the role of HDL in atherogenesis and thrombosis. The investigation of naturally occurring genetic variants affecting lipoprotein and HDL metabolism has provided insights into the relevance of specific apolipoproteins and enzymes in these processes. This has been complemented in recent years by the creation of transgenic animals. The use of transgenic animals has confirmed older hypotheses regarding the function of HDL but, as yet, has contributed few conceptually novel ideas.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The eicosanoids are a series of oxygenated derivatives of arachidonic acid and other similar polyunsaturated fatty acid precursors. The term encompasses prostaglandins, thromboxanes, leukotrienes, lipoxins and various hydroxy- and hydroperoxy-fatty acids. The major source of these derivatives are four enzyme-dependent pathways. However, recent evidence suggests that they may also be formed by a non-enzymatic, free radical-catalysed mechanism. Several of the eicosanoids are potent regulators of vascular tone. They also modulate the function of circulating platelets and cells of the arterial wall. These properties suggest that the eicosanoids may also play a role in atherogenesis, and this is supported by a number of intervention trials in which drugs that alter eicosanoid metabolism have been used to prevent atherosclerosis and/or modify clinically more obvious events such as thrombosis and myocardial infarction. In this article, we have reviewed some of the most recent evidence for a role of the eicosanoids in atherogenesis.

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1993

数据来源: OVID