Oxidized LDL density lipoprotein antibodies and oxidized low density lipoprotein-containing immune complexes: Characteristics and pathogenic significance in diabetes.

摘要

Mounting evidence suggests that two major vascular complications of diabetes mellitus, atherosclerosis and nephropathy, are pathogenically analogous processes, with atherosclerosis occurring primarily in the macrovasculature and nephropathy involving the microvasculature. Additionally, several lines of evidence point to oxidized low-density lipoprotein (oxLDL) as a major participant in both processes. Previous work in our laboratory has focused on the immunogenicity of oxLDL, and we have shown that heterogeneous LDL-containing immune complexes (LDL-IC), made with human LDL and rabbit LDL-hyperimmune antisera, are unmatched in their ability to drive the transformation of human monocyte-derived macrophages into foam cells. Recently, we undertook a three-part endeavor to better understand the pathogenic role of LDL-IC in microvascular and macrovascular complications of diabetes. Our goals were to (1) further characterize oxLDL antibodies that we isolated from serum and immune complexes; (2) considering the similarities between nephropathy and atherosclerosis, we wished to determine if LDL-IC are associated with diabetic nephropathy, as is observed in macrovascular disease; (3) determine if artificially prepared homogeneous oxLDL-IC, made with oxLDL and human oxLDL antibodies, produce similar results in macrophages to those observed with the use of heterogeneous LDL-IC.; In conclusion, these findings demonstrate a positive association of diabetic microvascular disease and LDL-ICs that is reminiscent of that observed between LDL-IC and macrovascular disease. We have shown that homogeneous oxLDL-IC causes foam cell formation in macrophages, therefore are likely participants in microvascular (nephropathy) and macrovacular (atherosclerosis) diseases processes. Lastly, we have validated the continued use of heterogeneous LDL-ICs in studies of macrophage: LDL-IC interactions. (Abstract shortened by UMI.)