Antibodies to oxidized LDL in atherosclerosis development--clinical and animal studies

Abstract

Atherosclerotic lesions represent the principal cause of death in western industrialized countries. Immune mechanisms have been suggested to play a key role in the development of atherosclerosis. Several lines of evidence support that oxidized LDL (oxLDL) may be a key antigen in atherosclerosis. Antibodies to oxLDL have been found in human and rabbit plasma and in atherosclerotic lesions. So far, it has not been well established if the immune response is predominantly pro- or antiatherogenic. During the last decade, numerous studies have been performed investigating the relationship between circulating antibodies in plasma in relation to endothelial dysfunction, subclinical atherosclerosis and cardiovascular events in different patient categories. Taken together, these studies have shown diverging results. However, most studies have shown that elevated IgG titers to oxLDL are related to atherosclerotic disease. Even if fewer studies have investigated IgM titers, most studies seem to show an inverse relationship between IgM titers and atherosclerotic disease. In animal studies, it has been shown that immunization with oxLDL induces antibody formation (both IgG and IgM) and protects against atherosclerosis development. Furthermore, it has also been shown that immunization with Streptococcus pneumoniae induce an IgM response, which is associated with decreased atherosclerosis development, and plasma from these mice also has the ability to block uptake of oxLDL to macrophages. To conclude, antibodies to oxLDL in clinical cardiovascular disease show diverging results, while animal studies suggest that immunization may have a beneficial role in atherosclerosis development. Prospective and intervention studies, as well as mechanistic studies are clearly needed to elucidate the possible causal role of antibodies to oxLDL in man.