The inverse correlation between serum levels of high density lipoprotein (HDL) cholesterol
and the risk of coronary heart disease, the protection of susceptible animals from
atherosclerosis by transgenic manipulation of HDL metabolism, and several potentially
anti-atherogenic in vitro-properties have made HDL metabolism an interesting target
for pharmacological intervention in atheroslcerosis. We have previously reviewed the
concept of reverse cholesterol transport, which describes both the metabolism and
the classic anti-atherogenic function of HDL (Arterioscler. Thromb. Vasc. Biol. 20
2001 13). We here summarize the current understanding of additional biological, potentially
anti-atherogenic properties of HDL. HDL inhibits the chemotaxis of monocytes, the
adhesion of leukocytes to the endothelium, endothelial dysfunction and apoptosis,
LDL oxidation, complement activation, platelet activation and factor X activation
but also stimulates the proliferation of endothelial cells and smooth muscle cells,
the synthesis of prostacyclin and natriuretic peptide C in endothelial cells, and
the activation of proteins C and S. These anti-inflammatory, anti-oxidative, anti-aggregatory,
anti-coagulant, and pro-fibrinolytic activities are exerted by different components
of HDL, namley apolipoproteins, enzymes, and even specific phospholipids. This complexity
further emphasizes that changes in the functionality of HDL rather than changes of
plasma HDL-cholesterol levels determine the anti-atherogenicity of therapeutic alterations
of HDL metabolism.