Cholesterol efflux pathways and other potential mechanisms involved in the athero‐protective effect of high density lipoproteins
Abstract
Plasma high density lipoprotein (HDL) levels bear a strong independent inverse relationship with atherosclerotic cardiovascular disease. Although HDL has anti-oxidant, anti-inflammatory, vasodilating and anti-thrombotic properties, the central anti-atherogenic activity of HDL is likely to be its ability to remove cholesterol and oxysterols from macrophage foam cells, smooth muscle cells and endothelial cells in the arterial wall. To some extent, the pleotropic athero-protective properties of HDL may be related to its ability to promote sterol and oxysterol efflux from arterial wall cells, as well as to detoxify oxidized phospholipids. In cholesterol-loaded macrophages, activation of liver X receptors (LXRs) leads to increased expression of adenosine triphosphate (ATP) binding cassetter transporter (ABCA1), ATP binding cassetter transporter gene (ABCG1) and apoE and promotes cholesterol efflux. ABCA1 stimulates cholesterol efflux to lipid-poor apolipoproteins, whilst ABCG1 promotes efflux of cholesterol and oxysterols to HDL. Despite some recent setbacks in the clinical arena, there is still intense interest in therapeutically targeting HDL and macrophage cholesterol efflux pathways, via treatments with niacin, cholesterol ester transfer protein inhibitors, LXR activators and infusions of apoA-1, phospholipids and peptides.
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LXR activation induces HDL particle formation through apoe and abca1 expression.
“LXR activation induces HDL particle formation through apoe and abca1 expression (Lehmann et al., 1997; Tall, 2008).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Tall, 2008
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- Authors
- Tall, A. R.
- Affiliations
- Columbia University (US)
- Corresponding author
- Tall, A. R.
- ORCID
- Tall, A. R.
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2008-02-04
- Volume
- 263
- Issue
- 3
- Pages
- 256-273
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- OpenAlex
- W2076021360
- Cited by
- 436
- References
- 3
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 19 · 2020: 20 · 2019: 17 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 28 · 2014: 28 · 2013: 47 · 2012: 33
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- high-density lipoprotein, cholesterol efflux, atherosclerosis, liver X receptor, ABCA1, ABCG1, apolipoprotein E, oxysterols, foam cells, HDL-targeted therapy, nicotinic acid, cholesterol ester transfer protein inhibitors, apolipoprotein A-I, oxidized phospholipids
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily G, Member 1, Biological Transport, Cholesterol, Humans, Lipoproteins, HDL, Macrophages, ATP-Binding Cassette Transporters, Atherosclerosis, ATP Binding Cassette Transporter 1
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