Structural Modifications of HDL and Functional Consequences
Abstract
High density lipoproteins (HDL) are susceptible to structural modifications mediated by various mechanisms including oxidation, glycation, homocysteinylation or enzymatic degradation. Structural alterations of HDL may affect their functional and atheroprotective properties. Oxidants, such as hypochlorous acid, peroxyl radicals, metal ions, peroxynitrite, lipoxygenases and smoke extracts, can alter both surface and core components of HDL. The formation of lipid peroxidation derivatives, such as thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and aldehydes, is associated with changes of physical properties (fluidity, molecular order) and of apoprotein conformation. Non-enzymatic glycation, generally associated with lipoxidation, leads to form irreversible complexes called advanced glycation end products. These HDL modifications are accompanied with altered biological activities of HDL and associated enzymes, including paraoxonase, CETP and LCAT. Homocysteine-induced modification of HDL is mediated by homocysteine-thiolactone, and can be prevented by a calcium-dependent thiolactonase/paraoxonase. Tyrosylation of HDL induces the formation of dimers and trimers of apo AI, and alters cholesterol efflux. Phospholipases and proteolytic enzymes can also modify HDL lipid and apoprotein structure. HDL modification induces generally the loss of their anti-inflammatory and cytoprotective properties. This could play a role in the pathogenesis of atherosclerosis and neurodegenerative diseases such as Alzheimer's disease.
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Ascorbic acid fosters anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.
“This vitamin has also been demonstrated to foster anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers [127,128,129].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [129]
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- Authors
- Ferretti, G., Bacchetti, T., Nègre-Salvayre, A., Salvayre, R., Dousset, N., & Curatola, G.
- Affiliations
- Inserm (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Ferretti, Gianna
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 184
- Issue
- 1
- Pages
- 1-7
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W2085222803
- Cited by
- 176
- References
- 70
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 2 · 2020: 9 · 2019: 11 · 2018: 3 · 2017: 9 · 2016: 5 · 2015: 9 · 2014: 9 · 2013: 9 · 2012: 6
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- high-density lipoprotein, HDL oxidation, lipid peroxidation, glycation, advanced glycation end products, homocysteine thiolactone, paraoxonase, cholesteryl ester transfer protein, lecithin:cholesterol acyltransferase, cholesterol efflux, anti-inflammatory activity, Alzheimer's disease, neurodegenerative diseases
- MeSH terms
- Antioxidants, Humans, Cholesterol, HDL, Lipid Peroxidation, Atherosclerosis
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