Structural modifications of HDL and functional consequences

• Published in: Atherosclerosis Vol. 184; no. 1; pp. 1 - 7
• Main Authors: Ferretti, Gianna, Bacchetti, Tiziana, Nègre-Salvayre, Anne, Salvayre, Robert, Dousset, Nicole, Curatola, Giovanna
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 2006; Elsevier
• Subjects: Antioxidants - therapeutic use; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation; Cardiology. Vascular system; Cholesterol, HDL - blood; Cholesterol, HDL - chemistry; Glycation; High density lipoprotein; Humans; Investigative techniques, diagnostic techniques (general aspects); Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; Medical sciences; Modification; Oxidation; Tobacco, tobacco smoking; Toxicology; Modification; High density lipoprotein; Oxidation; Glycation; Atherosclerosis; Calcium; Hypochlorous acid; Alzheimer disease; Pathogenesis; Lipids; Cardiovascular disease; Hydroperoxide; Esterases; Oxidant; Inorganic element; Vascular disease; Phosphoric triester hydrolases; Homocystein; Degenerative disease; Aryldialkylphosphatase; Lipoprotein HDL; Peroxidation; Trimer; Nervous system diseases; Thiol; Enzyme; Aldehyde; Biological activity; Cholesterol; Cerebral disorder; Sulfur containing aminoacid; Peptidases; Phospholipase; Apoproteins; Central nervous system disease; Hydrolases; Dimer; Oxidoreductases; Lipoxygenase
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2005.08.008

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.