ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The peroxisome-proliferator-activated receptor y is a member of the nuclear receptor superfamily that functions as a key transcriptional regulator of cell differentiation and lipid metabolism. In addition, peroxisome-proliferator-activated receptor y is now recognized to be the biological receptor for the thiazolidinedione class of antidiabetic drugs, which includes troglitazone and rosiglitazone. Recent evidence indicates that peroxisome-proliferator-activated receptor y is expressed at high levels in macrophages, including the foam cells of atherosclerotic lesions. Oxidized low-density lipoprotein, which plays a central role in lesion development, can activate peroxisome-proliferator-activated receptor y by providing the cell with oxidized fatty acid ligands of the receptor. The elucidation of a peroxisome-proliferator-activated receptor y signalling pathway in macrophages provides a mechanism by which oxidized lipids may directly regulate gene expression in the context of the atherosclerotic lesion. A number of potential target genes for peroxisome-proliferator-activated receptor y in these cells have been identified. Some, such as the type B scavenger receptor CD36 are induced by peroxisome-proliferator-activated receptor y ligands, whereas others, such as scavenger receptor type A, inducible nitric oxide synthetase and certain cytokines, are repressed. Given the widespread clinical use of thiazolidinediones, it is important to consider the influence of these drugs on the risk of atherosclerosis. The net effect of peroxisome-proliferator-activated receptor y ligands on the atherogenic process is likely to reflect a balance between local effects in the artery wall and systemic effects on lipid metabolism.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The scavenger receptor class B, type I (SR-BI) is an HDL receptor that mediates selective cholesterol uptake from HDL to cells. In rodents, SR-BI has a critical influence on plasma HDL-cholesterol concentration and structure, the delivery of cholesterol to steroidogenic tissues, female fertility, and biliary cholesterol concentration. SR-BI can also serve as a receptor for non-HDL lipoproteins and appears to play an important role in reverse cholesterol transport. Recent studies involving the manipulation of SR-BI expression in mice, either using adenovirus-mediated or transgenic hepatic overexpression or using homologous recombination for complete functional ablation, indicate that the expression of SR-BI protects against atherosclerosis. If SR-BI has a similar activity in humans, it may become an attractive target for therapeutic intervention.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The process of in-stent restenosis parallels wound healing responses. Stent deployment results in early thrombus deposition and acute inflammation, granulation tissue development, and ultimately smooth muscle cell proliferation and extracellular matrix synthesis. The severity of arterial injury during stent placement correlates with increased inflammation and late neointimal growth. These pathological findings provide useful targets for therapies aimed at reducing the incidence of in-Stent restenosis.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Recently, there has been a dramatic change in the way we think about the role of vascular smooth muscle cells in atherosclerosis, and it is now generally accepted that a dearth of vascular smooth muscle cells in an atherosclerotic plaque is a detrimental feature of the disease. Indeed, it is now recognized that the phenotypes of vascular smooth muscle cells within a plaque dictate its features, progression and stability. Therefore an understanding of the processes that generate and regulate vascular smooth muscle cell heterogeneity are of critical importance for future therapeutic advancement in the treatment of atherosclerosis.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

DNA arrays are revolutionizing the analysis of gene expression and single nucleotide polymorphisms of genomic DNA. Currently, the expression of 10–15|X% of human genes can be analysed simultaneously in a single experiment using cDNA or oligonucleotide-based format of DNA array. Alternatively, smaller DNA arrays with a limited number of selected genes, such as cytokines, growth factors or transcription factors, can be used. In concordance with Human Genome Project, after a few years, the DNA arrays will allow the analysis of expression of the whole human genome and will have a great impact on basic research, drug development and diagnostics. It is important to characterise mechanisms of atherosclerosis-related diseases at the level of gene expression so that new therapeutic strategies can be identified. With the aid of DNA array it is possible to identify multiple, simultaneous, transcriptional events that ameliorate or contribute to atherogenesis. The results are non-physical maps of the function, hierarchy and interactions of genetic programs. In this review we focus on DNA array technology and its applications in atherosclerosis research.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Large randomized placebo-controlled trials have demonstrated that cholesterol lowering with statin therapy reduces the incidence of adverse cardiac events. Smaller angiographic studies have shown that coronary artery disease progression can be slowed and, in some cases, reversed by cholesterol-lowering interventions. These anatomical changes, however, are small and occur too slowly to account for the early clinical benefit. Current evidence suggests that plaque stabilization is the most important mechanism, by which cholesterol-lowering therapy reduces both the incidence of adverse cardiac events and coronary artery disease progression.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The results of recent trials indicate that statin treatment reduces not only the risk of coronary heart disease, but also the risk of stroke, in patients with existing heart disease. The need for the treatment of such patients is now generally recognized. Mechanisms for risk reduction include the retardation of plaque progression, plaque stabilization, and reducing the risk of coronary events. Questions remain regarding the discrepancy between epidemiological data and statin trials data, the precise mechanism of action of statins, and their role in the prevention of recurrent stroke in individuals who have experienced a previous stroke or transient ischemic attack but are free of coronary disease.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Statins have pleiotropic properties that complement their cholesterol-lowering effects. These properties may partly account for their established benefit in the prevention of coronary artery disease beyond the reduction of LDL-cholesterol levels. The most widely recognized properties are reviewed here. They include: (i) nitric oxide-mediated improvement of endothelial dysfunction and upregulation of endothelin-1 expression; (ii) antioxidant effects; (iii) anti-inflammatory properties; (iv) inhibition of cell proliferation with anticarcinogenic actions in animals; (v) stabilization of atherosclerotic plaques; (vi) anticoagulant effects; and (vii) inhibition of graft rejection after heart and kidney transplantation. As advances are made in our knowledge, new properties are steadily being uncovered. Pleiotropic effects are currently being given consideration when instituting combination therapy for patients at high cardiovascular risk. Some pleiotropic effects are negative, and may account for occasional untoward drug interactions. For many of these new properties, the clinical relevance has not been established. The challenge for the future will be to design and carry out appropriate clinical trials to establish their relative importance in the prevention of coronary artery disease.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID