HDL metabolism and atherosclerosis.
Epidemiologic studies of recent years have demonstrated an association between low plasma high-density lipoprotein (HDL) cholesterol levels and the development of atherosclerosis. The PROCAM (Prospective Cardiovascular Münster) study has identified HDL cholesterol as the single parameter predictor with the highest potency. Also, in multiple logistic function analysis of these data, which included the eight best independent predictors, HDL cholesterol contributed the largest portion to the overall predictive power of the algorithm. Further evidence for the important role of HDL in the atherosclerotic process was provided by the Helsinki Heart Study, in which the lipid-lowering and HDL-increasing drug gemfibrozil was effective in reducing CAD incidences. In cohort studies, we have shown that HDL cholesterol concentrations largely differ between CAD patients and sex- and age-matched unaffected controls and that this difference increases with age. The reverse cholesterol transport hypothesis is the most widely used to explain the biochemistry of HDL-mediated atherosclerosis. In fact, it has been shown that HDL mediates the disposal of excess cellular cholesterol. There is evidence for the existence of two different mechanisms by which HDL can take up cellular cholesterol: both involve specific cellular recognition sites and probably also different HDL subpopulations. At least two different mechanisms have been identified by which the HDL cholesterol is finally targeted to the liver: attachment of apolipoprotein E for direct recognition by liver receptors or lipid transfer to lipoproteins of lower density that are subsequently also recognized by internalizing liver receptors. This knowledge gives rise to many different candidate genes for the formation of HDL deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)
Assmann
G
G
Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, F.R.G.
Funke
H
H
D001161:Arteriosclerosis / Q000209:etiology*; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D008075:Lipoproteins, HDL / Q000172:deficiency / Q000378:metabolism*
D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL