OXIDATION-SPECIFIC EPITOPES IN HUMAN CORONARY ATHEROSCLEROSIS ARE NOTLIMITED TO OXIDIZED LOW-DENSITY-LIPOPROTEIN

Background Previous small studies have demonstrated positive immunohis tochemical staining in rabbit and human atherosclerotic plaques by ant ibodies that recognize oxidized low-density lipoprotein (OxLDL), but n one have examined a large number of human coronary arteries or evaluat ed whether epitopes recognized by these antibodies might be present on plaque proteins other than OxLDL. Methods and Results Immunohistochem istry was performed on atherosclerotic (n=87) and nonatherosclerotic ( n=51) coronary arterial segments from 20 patients by use of monoclonal antibodies chat recognize epitopes on macrophages, smooth muscle cell s, apolipoprotein (apo) B, and OxLDL. Staining with the OxLDL antibody (Ox5) was much more prevalent in atherosclerotic than in control segm ents. Extracellular Ox5 staining colocalized with apo B, but cell-asso ciated Ox5 staining occurred in the absence of cell-associated apo B s taining, which suggests that cell-associated epitopes for Ox5 were on proteins other than LDL. Epitopes for Ox5 formed in vitro on two readi ly available non-apo B proteins, human serum albumin and apo A-I, when these proteins were incubated under conditions of oxidant stress with polyunsaturated but not monounsaturated fatty acids; furthermore, an antioxidant inhibited Ox5 epitope formation. Thus, epitopes for Ox5 ca n form on proteins other than apo B. Also, phorbol ester-treated macro phages cultured in apo B-free medium developed epitopes for Ox5. Concl usions These findings are consistent with the hypothesis that atherosc lerosis is associated with oxidative modification of proteins in addit ion to LDL, particularly cell-associated proteins, and that the antiat herosclerotic effects of antioxidants seen in some studies may not be solely due to prevention of LDL oxidation.