IN-VIVO OXIDIZED LOW-DENSITY-LIPOPROTEIN - DEGREE OF LIPOPROTEIN OXIDATION DOES NOT CORRELATE WITH ITS ATHEROGENIC PROPERTIES

We have recently demonstrated that lipids, particularly cholesterol, c ovalently bound to apolipoprotein B (apoB) are a stable marker of low density lipoprotein (LDL) oxidation (Tertov et nl. 1995). The present study is an attempt to assess the relationship between the degree of L DL oxidation, evaluated by the content of apoB-bound cholesterol and t he ability of LDL to induce cholesterol accumulation in cultured human aortic intimal smooth muscle cells, i.e. LDL atherogenicity. Native L DL was oxidized in vitro by copper ions, 2,2-azobis-(2-aminopropane hy drochloride), or sodium hypochlorite. Minimum degree of LDL in vitro, oxidation necessary to convert LDL into atherogenic one was accompanie d by an increase of apoB-bound cholesterol to the level much higher th an that usually observed in freshly isolated atherogenic LDL from huma n blood. Moreover, elimination of LDL aggregates from in vitro oxidize d LDL preparations by gel filtration led to loss of its atherogenic pr operties. Thus, the ability to induce cholesterol accumulation in cell s, i.e. the atherogenicity of in vitro oxidized LDL is a result of LDL aggregation but not oxidation. We also studied the relationship betwe en LDL atherogenicity and apoB-bound cholesterol content in LDL freshl y isolated from healthy subjects and normo-and hypercholesterolemic pa tients with coronary atherosclerosis. The ability of human LDL to indu ce cholesterol accumulation in aortic smooth muscle cells did not corr elate with the degree of in vivo LDL oxidation (r = 0.12, n = 90). It is concluded that LDL atherogenicity does not depend on the degree of lipid peroxidation in LDL particle.