High-density lipoproteins: the guardian angel of the cell membrane

Abstract

High-density lipoproteins (HDL) plasma levels are inversely correlated with the risk of atherosclerosis and coronary heart disease. The protective effect of HDL has been related to their role in the cholesterol reverse transport and to their ability to inhibit oxidation of low-density lipoproteins (LDL). Several lines of evidence suggest that the protective effect of HDL is at least partially related to the enzyme paraoxonase (PON1), a calcium-dependent esterase associated with the HDL surface. It has been hypothesised that PON1 may have two independent antiatherogenic roles: (a) by preventing the accumulation of oxidised lipids from oxidised lipoproteins (LDL and HDL) and thereby inhibiting the atherogenic and inflammatory response induced by lipid peroxidation products; (b) by detoxifying homocysteine thiolactone (HTL), a toxic metabolite of homocysteine. Recently, it has been reported that HDL-associated PON1 could also play a regulatory role in HDL binding to cell membranes and in HDL-mediated cholesterol efflux in macrophages. Several papers have reported that HDL are also able to protect and/or repair oxidative damage of cell membranes and we have recently demonstrated that the protective role of HDL is related to PON1 activity.