Current understanding of the metabolism and biological actions of HDL.
OBJECTIVE
A low concentration of HDL-cholesterol is an important risk factor for coronary heart disease. The purpose of this review is to summarize the novel functions of HDL that may protect not only from atherosclerosis, but also from inflammation-induced organ damage.


RESULTS
HDL interacts with several cellular receptors and lipid transporters. The interactions of HDL or apolipoprotein A-I with the scavenger receptor BI or adenosine triphosphate binding cassette transporters A1, G1 and G4 induce cholesterol efflux. Apolipoproteins and enzymes carried by HDL exert antioxidative functions. Some oxidative modifications of apolipoprotein A-I, for example of tyrosine residues, may however interfere with anti-atherosclerotic activities. The interactions of HDL and lysosphingolipids therein with scavenger receptor BI and sphingolipid receptors, respectively, elicit signals activating the protein kinase Akt, which in turn is a regulator of apoptosis in beta, endothelial and smooth muscle cells as well as a regulator of nitric oxide production and adhesion molecule expression in endothelial cells. Other signal transduction cascades are also elicited by HDL, some of which induce cholesterol efflux or activate mitogen-activated protein kinases.


CONCLUSIONS
Properties with respect to cytokine production, lipid oxidation, cholesterol efflux and reverse cholesterol transport make HDL a protective agent and thus an interesting therapeutic target in atherosclerosis and inflammation-induced organ damage.
von Eckardstein
Arnold
A
Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, CH 8091 Zurich, Switzerland. arnold.voneckardstein@usz.ch
Hersberger
Martin
M
Rohrer
Lucia
L
D001161:Arteriosclerosis / Q000378:metabolism* / Q000517:prevention & control; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D010084:Oxidation-Reduction
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D002784:Cholesterol