Advances in lipid research最新文献

When DeLalla and Gofman (1954) presented their work "Ultracentrifugal Analysis of Serum Lipoproteins" more than 25 years ago, we were thinking about lipoproteins in terms of density fractions. In the 1970s the electrophoresis concept was pushed by Fredrickson and his colleagues (Fredrickson et al., 1967). There is no doubt that both these lipoprotein research centers have fertilized entire investigations in this field and still have a tremendous impact on our current knowledge. It was, however, not until 1966, when Gustafson, Alaupovic, and Furmann first described the presence of a third lipoprotein family, LpC, that researchers in this area became aware of the dominant role of apolipoproteins in the transport and metabolism of plasma lipids. Lipoprotein density fractions and electrophoretic classes in the mean time have not lost their importance; they still exist and the application of methods yielding those fractions is still going on in lipoprotein laboratories. Yet we need to recognize that the whole lipid transport system is far more complex than was believed some 10 or 20 years ago. Lipoprotein density fractions consist of varying numbers of families; some of them comigrate upon electrophoresis, and the protein moiety of them is mostly composed of nonidentical polypeptides. There are a number of inborn errors of metabolism, for example, ABL, Tangier disease, and enzyme defects, which have taught us a lot about the functions and interplay of the complex apolipoprotein system. In dyslipoproteinemia, abnormal lipoproteins occur in the plasma and apolipoproteins, which are hardly recognized in normal fasting plasma, suddenly become prominent. There still exist, however, apolipoproteins and lipoproteins, one of which certainly is Lp(a), whose function and biological significance remains completely unknown. The structure and the molecular arrangement of lipids and apolipoproteins within a lipoprotein particle has been the subject of intensive investigations, and almost every physicochemical method available has been applied to reveal the morphology of individual lipoproteins in closest detail. Lipoproteins and apolipoproteins have often also served as model substances for cell membranes. After the purification of individual apolipoproteins succeeded in many laboratories and specific antibodies were available, clinical chemists and epidemiologists became interested in this area of research. Apolipoprotein quantification currently is most prominent for the prediction of atherosclerotic risk in preventive medicine.(ABSTRACT TRUNCATED AT 400 WORDS)

Nicotinic acid is used widely in the treatment of hyperlipoproteinemias and reduces both the cholesterol and the triglyceride concentrations in the plasma. However, very high doses are needed to achieve these therapeutic effects, which is why side effects are common and are particularly known to hinder the compliance of patients. Nicotinic acid derivatives have been developed to overcome this problem. As a result of chemical and galenic retardation, these derivatives lessen the side effects and the necessary doses are considerably reduced in comparison with pure nicotinic acid. However, most of these derivatives are not pure prodrugs, and exert their own synergistic pharmacokinetic and pharmacodynamic effects. In general, when nicotinic acid and its derivatives are used in therapy a desirable modification of the composition of the plasma lipids in the sense of an antiatherosclerotic activity can be expected (reductions of VLDL and LDL and an increase of HDL). Good possibilities for using nicotinic acid in the prevention and remission of atherosclerotic processes arise in connection with the activation of fibrinolysis and the reduction of the tendency toward platelet aggregation. In the light of recent studies on the mechanisms of action of nicotinic acid, an influence on the prostaglandin system has been found, as a result of which an interconnection between its various effects and side effects appears to be possible.