ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

This article is an edited excerpt from the author's book entitled 'Hammersmith Marathon', published by Royal Society of Medicine Press, London

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Apolipoprotein E is a key regulator of plasma lipid levels. Our appreciation of its role continues to expand as additional aspects of its function are discovered. Apolipoprotein E affects the levels of all lipoproteins, either directly or indirectly by modulating their receptor-mediated clearance or lipolytic processing and the production of hepatic very low density lipoproteins. Furthermore, it plays a critical role in neurobiology. The apolipoprotein E4 allele is the major susceptibility gene related to the occurrence and early age of onset of Alzheimer's disease. It is probable that one of the major functions of apolipoprotein E in the central nervous system is to mediate neuronal repair, remodeling, and protection, with apolipoprotein E4 being less effective than the E3 and E2 alleles. The isoform-specific effects of apolipoprotein E are currently being unraveled through detailed structure and function studies of this protein.

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:

Lipoprotein(a) is an atherogenic, cholesterol ester-rich lipoprotein of unknown physiological function. The unusual species distribution of lipoprotein(a) and the extreme polymorphic nature of its distinguishing apolipoprotein component, apolipoprotein(a), have provided unique challenges for the investigation of its biochemistry, genetics, metabolism and atherogenicity. Some fundamental questions regarding this enigmatic lipoprotein have escaped elucidation, as will be highlighted in this review.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Further understanding of the causative link between plasma lipids and coronary heart disease will come from a deeper appreciation of the impact of lipoprotein heterogeneity on the processes of atherosclerosis and thrombosis. It is now widely appreciated that remnants of triglyceride-rich lipoproteins, IDL and specific LDL subfractions may have a role in atherogenesis disproportionate to the plasma concentrations of these species. Elucidation of the factors that control the distribution of subfractions within the spectrum of apolipoprotein B-containing lipoproteins is underway but far from complete. Important influences are the rate and nature of lipoproteins secreted from the liver, the extent of remodelling by lipid exchange and lipolysis in the circulation and the affinity of the various particles for cell Surface receptors.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The peroxisome proliferator-activated receptors (PPARs) [alpha, delta (beta) and gamma] form a subfamily of the nuclear receptor gene family. All PPARs are, albeit to different extents, activated by fatty acids and derivatives; PPAR-alpha binds the hypolipidemic fibrates whereas antidiabetic glitazones are ligands for PPAR-gamma. PPAR-alpha activation mediates pleiotropic effects such as stimulation of lipid oxidation, alteration in lipoprotein metabolism and inhibition of vascular inflammation. PPAR-alpha activators increase hepatic uptake and the esterification of free fatty acids by stimulating the fatty acid transport protein and acyl-CoA synthetase expression. In skeletal muscle and heart, PPAR-alpha increases mitochondrial free fatty acid uptake and the resulting free fatty acid oxidation through stimulating the muscle-type carnitine palmitoyltransferase-I. The effect of fibrates on the metabolism of triglyceride-rich lipoproteins is due to a PPAR-alpha dependent stimulation of lipoprotein lipase and an inhibition of apolipoprotein C-III expressions, whereas the increase in plasma HDL cholesterol depends on an overexpression of apolipoprotein A-I and apolipoprotein A-II. PPARs are also expressed in atherosclerotic lesions. PPAR-alpha is present in endothelial and smooth muscle cells, monocytes and monocyte-derived macrophages. It inhibits inducible nitric oxide synthase in macrophages and prevents the IL-1-induced expression of IL-6 and cyclooxygenase-2, as well as thrombin-induced endothelin-1 expression, as a result of a negative transcriptional regulation of the nuclear factor-κB and activator protein-1 signalling pathways. PPAR activation also induces apoptosis in human monocyte-derived macrophages most likely through inhibition of nuclear factor-κB activity. Therefore, the pleiotropic effects of PPAR-alpha activators on the plasma lipid profile and vascular wall inflammation certainly participate in the inhibition of atherosclerosis development observed in angiographically documented intervention trials with fibrates.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Hepatic lipase catalyses the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Genetic deficiency of this enzyme is associated with a unique plasma lipoprotein profile, characterized by hypertriglyceridemia and elevated concentrations of intermediate density lipoproteins and HDL. Recent studies have identified common polymorphisms in the hepatic lipase gene that are associated with low hepatic lipase activity-and increased concentrations of large HDL. Association studies using these polymorphisms are elucidating the effects of variation in hepatic lipase activity on plasma lipoprotein concentrations and susceptibility to coronary atherosclerosis.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Based on an improved molecular understanding of how bile acid metabolism is regulated, an exciting period of research developments can be expected. By new ways of stimulating cholesterol breakdown to bile acids, novel therapeutic principles can be forseen which will further improve our potential for treating and preventing atherosclerosis.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Our understanding of the genetics, metabolism and pathophysiology of the atherogenic plasma lipoprotein Lp(a) has considerably increased over past years. Nevertheless, the precise mechanisms regulating the biosynthesis and assembly of Lp(a) are poorly understood and controversially discussed. Lp(a) plasma concentrations are determined by synthesis and not by degradation. Transcriptional and post-translational mechanisms have been identified as regulating Lp(a) production in primary hepatocytes and transfected cell lines. Assembly of Lp(a) occurs extracellularly from newly synthesized apolipoprotein(a) and circulating LDL. This view has recently been challenged by in-vivo kinetic studies in humans which are compatible with an intracellular assembly event. Lp(a) assembly is a complex two-step process of multiple non-covalent interactions between apolipoprotein(a) and apolipoprotein B-100 of LDL followed by covalent disulfide linkage of two free cysteine residues on both proteins.

ISSN:0957-9672    

出版商:OVID    

年代:1999

数据来源: OVID