Oxidative modification of low-density lipoprotein (EDL) enhances its uptake by macrophaps in tissue culture and in vivo may underly the formation of arterial fatty streaks. the progenitors of atheroma. We investigated the possible protection which high-density lipoprotein (HDL) affords against LDL oxidation. The formation of lipoperoxides and thiobarbituric acid reactive substances when LDL was incubated with copper ions was significantly decreased by HDL. The enzyme, paraoxonase (E.C. 3.1.&l), purified from human HDL, had a similar effect and thus may be the component of HDL responsible for decreasing the accumulation of lipid peroxidation products.

No abstract

No abstract

Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low density lipoprotein (LDL) against oxidative modification, which has led to the proposal that PON1 is an antiatherogenic, anti-inflammatory enzyme. PON1 has two genetically determined polymorphic sites giving rise to amino-acid substitutions at positions 55 (LC CM) and 192 (RC CQ) and therefore 4 potential alloenzymes. We have examined the effects of these molecular polymorphisms on the ability of HDL to protect LDL from oxidative modification. HDL protected LDL from oxidative modification, whatever the combination of PON1 alloenzymes present in it. However, HDL from QQ/MM homozygotes was most effective at protecting LDL while HDL from RR/LL homozygotes was least effective. Thus after 6 h of co-incubation of HDL and LDL with Cu P+