Antibody to oxidized low-density lipoprotein inhibits THP1 cells from apoptosis by suppressing NF-κB pathway activation

Cardiovascular diseases, including acute coronary syndromes (ACS), have been the leading cause of morbidity and mortality worldwide. The major pathological process underlying these cardiovascular events is the atherosclerosis, a chronic inflammatory and immune disease occurring in response to the injury in blood vessel wall (1,2). Atherosclerotic plaques contain macrophage-derived foam cells in which macrophages interact with T-cells to produce a wide array of cytokines exerting both pro- and anti-inflammatory effects (1,3,4). Circulating oxidized low-density lipoprotein (Ox-LDL) antibody is almost detectable in all the patients with atherosclerosis, and the concentration of Ox-LDL antibody seems to be associated with the onset of clinical disease. Numerous studies have investigated the association between circulating Ox-LDL antibody and cardiovascular disease, but there is still controversy on this issue. Some studies show a positive correlation between circulating Ox-LDL antibody and atherosclerotic diseases, whereas others reveal a negative relationship (5-11). The reasons for this discrepancy are still unknown, and some investigators ascribe it to the difference in the standardization of LDL antigens used for the testing of Ox-LDL antibody, which may be altered on account of oxidation ex vivo (7). A resolution to this issue is the detection of antibody against specific native or MDA-modified ApoB100 peptide (12,13). ApoB100 is the only component permanently associated with the LDL formation in the body. Its peptide fragments generated by the proteolytic degradation and aldehyde-modification are the major antigens in Ox-LDL (14). These antigens have the unique amino acid sequence indicating their specificity. The mature ApoB100 protein is composed of 4,563 amino acids in a single polypeptide and carries many human leukocyte antigen (HLA)-restricted epitopes (14)