Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells

Abstract

Objective-Both advanced glycosylation end products (AGEs) and dendritic cells (DCs) have been shown to play a causative role in atherosclerosis. However, whether they function interactively in the process remains uncertain. We therefore studied the effects of AGE-bovine serum albumin (AGE-BSA) on the maturation of DCs and the expressions of scavenger receptor-A (SR-A) and receptor for AGEs (RAGE) on DCs. Key Words: advanced glycosylation end products Ⅲ atherosclerosis Ⅲ dendritic cells Ⅲ immunity Ⅲ receptor for advanced glycosylation end products D iabetes is associated with severe atherosclerosis and cardiovascular diseases that account for a high mobility and mortality in industrialized countries. 1 It is therefore very important for us to understand the mechanisms of how the diseases occur. Advanced glycosylation end products (AGEs) (long-term products of the Maillard reaction) have been shown to play a causative role in diabetic vasculopathy and atherosclerosis. 2,3 In diabetic atherosclerotic lesions, not only the deposition of AGEs but also the colocalization of AGEs antigen and AGEs receptors (scavenger receptor A [SR-A], receptor for AGEs [RAGE]) were found. 2,3 Additionally, accumulating evidences have suggested that dendritic cells (DCs) also play a crucial role in atherosclerosis 4 by activating T-cell in atherosclerosis. 5 Proinflammatory factors can promote maturation of DCs corresponding to a switch from a phagocytic stage to a stage of strong T cell-stimulatory capacity. The interactive roles of AGEs and DCs remain unknown now. We therefore examined the effect of advanced glycosylation end-bovine serum albumin (AGE-BSA) on DCs maturation, cytokine secretion, and SR-A and RAGE expression. MethodsThe informed consent was obtained from all volunteers and the study protocol was approved by our institutional ethical committee.

Receptor for Advanced Glycation End Products Expression on T Cells Contributes to Antigen-Specific Cellular Expansion In Vivo

“…5A). These findings were surprising because recent studies have noted that the RAGE ligand HMGB-1 is released from DCs and can contribute to DC maturation and function (21) after RAGE and/or TLR2, -4, and -9 engagement (13,19,(22)(23)(24). However, the data reported here reveal that RAGE Ϫ/Ϫ BMDCs and splenic DCs responded normally to TLR stimulation, up-regulating surface expression of both CD86 and MHC class II and secreting normal levels of immunostimulatory cytokines.…”

Advanced Glycation End Products Inhibit Both Infection and TransmissionIn Transof HIV-1 from Monocyte-Derived Dendritic Cells to Autologous T Cells

“…Indeed, Price et al (58) observed a dosedependent inhibition of CD83 expression on DCs exposed to AGE peptide, associated with the loss of their capacity to stimulate primary proliferation of allogeneic T cells. In contrast, Ge et al (31) have shown that AGE induced a dose-and time-dependent maturation of DCs as indicated by the expression of CD83. This apparent discrepancy could be explained by the use in this study of anti-CD14 Ab-coated beads to purify monocytes and, above all, much higher AGE concentrations (up to 200 mg/l).…”

“…The best-characterized receptor for AGEs, RAGE, is expressed on many cells that are targeted by HIV-1, such as monocytes and macrophages (27,28), CD4 T cells, and dendritic cells (DCs) (29)(30)(31). In monocytes and DCs, RAGE activation leads to an increase in proinflammatory cytokines such as IL-1b or TNF-b (32), IFN-g, and several chemokines and growth factors (31,(33)(34)(35). Considering the contribution of these factors to HIV-1 infection, AGE-RAGE interactions are likely to impact the biology of HIV-1 infection in many ways.…”

Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor γ activation

“…It has been well documented that AGE and its receptor (RAGE) axis is involved in the pathogenesis of cardiovascular disease due to oxidative stress and inflammatory responses (4)(5)(6)(7). Furthermore, impaired macrophage lipid metabolism directly participates in foam cell formation in diabetes (8,9).…”