Modified HDL: biological and physiopathological consequences.

Epidemiological and clinical studies have demonstrated the inverse association between HDL cholesterol levels (HDL-C) and the risk of coronary heart disease (CHD). This correlation is believed to relate to the ability of HDL to promote reverse cholesterol transport. Remodeling of HDL due to chemical/physical modifications can dramatically affect its functions, leading to dysfunctional HDL that could promote atherogenesis. HDL modification can be achieved by different means: (i) non-enzymatic modifications, owing to the presence of free metal ions in the atherosclerotic plaques; (ii) cell-associated enzymes, which can degrade the apoproteins without significant changes in the lipid moiety, or can alternatively induce apoprotein cross-linking and lipid oxidation; (iii) association with acute phase proteins, whose circulating levels are significantly increased during inflammation which may modify HDL structure and functions; and (iv) metabolic modifications, such as glycation that occurs under hyperglycaemic conditions. Available data suggest that HDL can easily be modified losing their anti-atherogenic activities. These observation results mainly from in vitro studies, while few in vivo data, are available. Furthermore the in vivo mechanisms involved in HDL modification are ill understood. A better knowledge of these pathways may provide possible therapeutic target aimed at reducing HDL modification.