摘要:

Vascular gene transfer may be useful for the treatment of several cardiovascular diseases. It can also be used as an experimental tool to test the effects of various genes in a local vascular compartment. Promising therapeutic effects have been obtained in animal models of restenosis with the transfer of vascular endothelial growth factor, nitric oxide synthase, thymidine kinase, retinoblastoma, growth arrest homeobox gene, cyclin/cyclin-dependent kinase inhibitor (p21), and hirudin genes, and antisense oligonucleotides against transcription factors or cell cycle regulatory proteins. Vascular endothelial growth factor and fibroblast growth factor gene transfers have improved blood flow and capillary development in models of ischaemic limb and myocardium. First experiences of vascular endothelial growth factor gene transfer to human peripheral arteries have also been reported. However, further developments in gene delivery techniques and gene transfer vectors will be required before a full therapeutic potential of gene therapy in cardiovascular diseases can be evaluated.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The dual function of lipoprotein lipase as a triglyceride hydrolase and a ligand/bridging factor for receptor-mediated lipoprotein uptake implies an important role of the enzyme in the distribution of fatty acids and lipoproteins among extrahepatic tissues. Observations in humans and, more recently, in several induced mutant mouse strains have provided important insights on how fat calories and lipids are partitioned to storage or energy production through the tissue-specific regulation of lipoprotein lipase in adipose tissue and muscle. Imbalances of the tissue-specific expression of lipoprotein lipase were recognized as potentially important effectors of lipoprotein metabolism, energy homeostasis and body weight regulation.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Familial combined hyperlipidaemia is a common cause of coronary heart disease. Its aetiology is heterogeneous. The genetic and metabolic basis of the disorder has not yet been defined. This review discusses the putative role of adipose tissue in the pathogenesis of familial combined hyperlipidaemia. It is possible that mutations in genes regulating the turnover of lipids in fat cells are involved in the aetiology.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To identify major genes influencing the complex disease process of atherosclerosis, the strategy for collection of study materials should be designed with care to enrich the genetic factors. The tools for an efficient gene search are provided by the Human Genome Program; current genetic maps with dense marker sets provide a basis for genome-wide scans, and close to complete physical maps and identification of coding regions of all human genes within next few years offer the scaffolding for the final recognition of genes predisposing to atherosclerosis. The statistical methods applicable in the initial gene search of complex diseases have developed during recent years including now exact modifications of association analysis, also advanced multipoint analyses applicable in both parametric (linkage analysis) and nonparametric (affected sib-pair) methods and maximizing the information extractable from individual genotypes. Genome scans in the relevant animal models will often guide to important genomic regions, and genetically modified animals will be of essential importance for final understanding of the molecular pathogenesis of atherosclerosis.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Plasma cholesteryl ester transfer protein facilitates the transfer of cholesteryl ester from HDL to apolipoprotein B-containing lipoproteins, and is a key protein in the reverse cholesterol transport system. The importance of plasma cholesteryl ester transfer protein in lipoprotein metabolism was highlighted by the discovery of deficient individuals with a marked hyper-HDL-cholesterolemia. Cholesteryl ester transfer protein deficiency causes various abnormalities in the concentration, composition, and functions of both HDL and LDL. Its significance in atherosclerosis is still controversial. However, in-vitro evidence shows large cholesteryl ester-rich HDL particles in cholesteryl ester transfer protein deficiency are defective in cholesterol efflux. Recent epidemiological studies have demonstrated an increased incidence of coronary atherosclerosis in deficient patients. The current review will also focus on the molecular genetics of the protein.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Oxidative modification converts LDL to an atherogenic form and 15-lipoxygenase has been implicated in this process. Several lines of experimental evidence support such a proatherogenic action of the enzyme. However, recent data obtained with transgenic rabbits overexpressing 15-lipoxygenase suggest also an antiatherogenic effect. In this paper the pathophysiological relevance of 15-lipoxygenase in atherogenesis is critically reviewed.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The plasminogen and coagulation systems have been extensively characterized at the biochemical level. Recent gene targeting and gene transfer studies have provided novel insights into their role in the formation of blood vessels and in the pathogenesis of blood vessel disorders including thrombosis, restenosis and atherosclerosis.

ISSN:0957-9672    

出版商:OVID    

年代:1997

数据来源: OVID