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HDL and arteriosclerosis: beyond reverse cholesterol transport
Jerzy-Roch Nofer1, Beate Kehrel, Manfred Fobker
1Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität, Albert Schweitzer Str. 33, 48129 Münster, Germany. nofer@uni-muenster.de
Insights
High-density lipoprotein (HDL) has multiple anti-atherogenic properties beyond cholesterol transport. HDL
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Inverse correlation between HDL cholesterol and coronary heart disease risk.
- HDL metabolism is a target for pharmacological intervention in atherosclerosis.
- Previous review covered reverse cholesterol transport and classic HDL anti-atherogenic function.
Purpose of the Study:
- Summarize current understanding of additional biological, potentially anti-atherogenic properties of HDL.
- Highlight the complexity of HDL's anti-atherogenic mechanisms.
- Emphasize HDL functionality over plasma levels for therapeutic impact.
Main Methods:
- Literature review and synthesis of existing research on HDL properties.
- Analysis of in vitro and in vivo studies on HDL's biological activities.
- Examination of HDL components responsible for various functions.
Main Results:
- HDL inhibits monocyte chemotaxis, leukocyte adhesion, endothelial dysfunction, apoptosis, LDL oxidation, complement activation, platelet activation, and factor X activation.
- HDL stimulates endothelial and smooth muscle cell proliferation, prostacyclin and natriuretic peptide C synthesis, and protein C and S activation.
- These diverse activities include anti-inflammatory, anti-oxidative, anti-aggregatory, anti-coagulant, and pro-fibrinolytic effects.
- Different HDL components (apolipoproteins, enzymes, phospholipids) mediate these functions.
Conclusions:
- HDL possesses numerous anti-atherogenic properties beyond cholesterol transport.
- HDL's complex functions are mediated by various components.
- Therapeutic strategies should focus on enhancing HDL functionality, not just cholesterol levels.
Abstract:
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.