HDL, ITS ENZYMES AND ITS POTENTIAL TO INFLUENCE LIPID-PEROXIDATION

In seeking an explanation of the inverse relationship between serum hi gh density lipoprotein (HDL) concentration and coronary heart disease (CHD) incidence, most investigations have been directed at its role in reverse cholesterol transport. However, recently it has become clear that HDL has the potential to limit oxidative modification of low dens ity lipoprotein (LDL) whether induced by transition metals or by cells in tissue culture. In view of the current theory that oxidative modif ication of LDL is an important element in atherogenesis, this suggests another potential mechanism by which HDL might impede the development of CHD. HDL is the major carrier of cholesteryl ester hydroperoxides, but more than this it appears to have the prolonged capacity to decre ase the total amount of lipid peroxides generated on LDL during oxidat ion while the quantity accumulating on HDL itself reaches an early pla teau. These effects are not explained by chain-breaking antioxidants p resent in HDL and are likely to involve an enzymic mechanism. Several enzymes are present on HDL: paraoxonase, lecithin:cholesterol acyl tra nsferase, platelet activating factor acetylhydrolase, phospholipase D and protease. Apolipoproteins, such as apolipoprotein AI, could also h ave enzymic activity. Evidence that some of these might act to metabol ise lipid peroxidation products, such as oxidised phospholipids and ly so-phosphatidylcholine, is discussed in this review.