Current understanding of the metabolism and biological actions of HDL
Abstract
Purpose of review 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. Recent findings 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. Summary 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. Abbreviations ABC: adenosine triphosphate binding cassette transporter; ATP: adenosine triphosphate; CETP: cholesteryl ester transfer protein; EGD: endothelial gene differentiation receptor; LXR: liver X receptor; NO: nitric oxide; PLTP: phospholipid transfer protein; RXR: retinoid X receptor; S1P: sphingosine-1-phosphate; SR-BI: scavenger receptor BI.
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Low levels of HDL are independently atherogenic.
“Finally, the lipoprotein field widely holds that low levels of HDL are independently atherogenic 1 ; multiple mechanisms are implicated to explain this relationship.90”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [90]
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- Authors
- Eckardstein, A. V., Hersberger, M., & Rohrer, L.
- Affiliations
- University Hospital Zurich (CH)
- Corresponding author
- Eckardstein, Arnold von
- Venue
- Current Opinion in Clinical Nutrition and Metabolic Care
- Published
- 2005-03
- Volume
- 8
- Issue
- 2
- Pages
- 147-152
- ISSN
- 1363-1950 (ISSN-L)
- OpenAlex
- W2057297878
- Cited by
- 155
- References
- 38
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 9 · 2022: 10 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 10
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Clinical Nutrition & Metabolic Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- HDL cholesterol, HDL metabolism, apolipoprotein A-I, scavenger receptor BI, ABC transporters, cholesterol efflux, reverse cholesterol transport, anti-atherosclerotic activity, Akt signaling, lysosphingolipids, nitric oxide, apoptosis, endothelial cells, atherosclerosis, coronary artery disease, HDL receptor
- MeSH terms
- Hypolipidemic Agents, Arteriosclerosis, Biological Transport, Cholesterol, Humans, Cholesterol, HDL, Oxidation-Reduction
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