title: [Role of anomalies of low density lipoproteins (LDL) in atherogenicity].
abstract: Qualitative and quantitative anomalies of low-density lipoproteins (LDL) play a key role in the pathophysiology of atherosclerosis. Such anomalies are characteristics of the atherogenic dyslipidemias which occur most frequently, i.e. primary hypercholesterolemia of phenotype IIA (including familial hypercholesterolemia), combined hyperlipidemias (Type IIB) and hypertriglyceridemia (Type IV). An elevated concentration of circulating LDL occurs either as a result of hepatic overproduction of VLDL particles, the major precursors of LDL, or as a result of delayed catabolism, as occurs when there is a deficit of cellular LDL receptors (e.g. familial hypercholesterolemia), or as a combination of both. The major qualitative anomaly of LDL which results in elevated atherogenicity involves a predominance of small dense LDL, as seen in patients with premature coronary heart disease and equally in combined hyperlipidemia and in hypertriglyceridemia. The mechanism of the formation of these particles is complex and involves the concerted intravascular action of cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL) and hepatic lipase (HL) on triglyceride-rich precursors of dense LDL Lipid-lowering agents, such as fibrates and statins, act to reduce the atherogenicity of dense LDL by distinct mechanisms, which lead to normalisation of circulating LDL levels and/or to targeted reduction in dense particles of elevated atherogenicity. Indeed, such pharmacological probes have facilitated new insight into the molecular and cellular mechanisms which underlie each of the major forms of atherogenic dyslipidemia.
authors.affiliation: INSERM U 321, CHU de La Pitié-Salpêtrière, Pavillon B. Delessert, 83 bld de l'hôpital-75651 Paris.
authors.forename: J M
authors.initials: JM
authors.lastname: Chapman
authors.forename: M
authors.initials: M
authors.lastname: Guérin
authors.forename: E
authors.initials: E
authors.lastname: Bruckert
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D008077:Lipoproteins, LDL / Q000097:blood / Q000502:physiology*
chemical_list: D008077:Lipoproteins, LDL