Lipoproteins are essential vehicles for conveyance of lipids and cholesterol in human metabolism. Apolipoprotein B100 (apoB100) is present in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). VLDL, IDL and chylomicrons deliver lipids to the peripheral cells and VLDL, IDL and LDL deliver cholesterol to the liver and peripheral tissue. Apolipoprotein A-1 (apoA1) is the major lipoprotein of high density lipoprotein (HDL). HDL conveys cholesterol ester from peripheral sites to the liver and thereby has anti-atherogenic activity. There are density subfractions of HDL: HDL1 (minor), HDL2 and HDL3; and also minor fractions of nascent ApoA1 and pre-β-HDL - forms that occur prior to lipid and cholesterol ester loading. Malfunction of ApoB100 and ApoA1 contribute to the development of cardiovascular disease (CVD) – the major cause of death in the human population worldwide. CVD is driven mainly by increased arterial atherosclerosis. Increased risk of atherosclerosis is associated with high levels of LDL and more particularly with high levels of small, dense LDL. Small, dense LDL has increased affinity for arterial proteoglycan and cell surface non-LDL receptor binding sites. Atherosclerosis is also driven by decreased levels of HDL. In ageing, the plasma half-life of LDL increases, leading to increased exposure of LDL to the oxidative environment of the plasma and extracellular fluid. In ageing also plasma levels of HDL decline. This is due to increased catabolism of apoA1 – mostly by destabilization of HDL2 and degradation in the kidney and liver. Atherogenicity of LDL increases and levels of HDL decrease with decline in glucose tolerance. Recent research has shown that damage to apoB100 by non-oxidative mechanisms produces atherogenic transformation of LDL to small, dense LDL which then binds with increased affinity to the arterial wall where it is susceptible to oxidation and accumulation in cells of atheromatous plaques. Similarly, non-oxidative damage to apoA1 of HDL may cause de-stabilization and increased catabolism. Such modifications increase in ageing as the rates of formation and rates of detoxification of modifying agents decline. The involvement of non-oxidative mechanisms in early-stage escalation of atherogenicity of LDL and de-stabilization of HDL may explain why antioxidant therapy has often been ineffective in early-stage prevention of CVD and point the way to new strategies for therapy.
Low density lipoprotein
High density lipoprotein