Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages

We investigated the effects of advanced glycation end products (AGEs) on th e expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only t he gene expression of two major OxLDL receptors, macrophage scavenger recep tor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-d ensity lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs i ncreased transcriptional activities of AP-1, NF-kappaB, and peroxisome prol iferator-activated receptor gamma. These findings indicate that AGEs-induce d enhancement of these transcriptional activities might be involved in incr eased levels of mRNA for some of OxLDL receptors in THP-1-cells treated wit h PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involve d in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of indivi duals with diabetes. (C) 2000 Academic Press.