Receptors for proteins modified by advanced glycation endproducts (AGE)--their functional role in atherosclerosis.
Long-term incubation of proteins with glucose leads, through the formation of early stage products such as Schiff base and Amadori rearrangement products, to the formation of advanced glycation end products (AGE). Recent studies of AGE-structures as well as the receptor for AGE-proteins (AGE-receptors) have emphasized the involvement of protein modification by AGE in aging and age-enhanced disease processes. Immunohistochemical analyses of human atherosclerotic lesions using a monoclonal anti-AGE antibody have demonstrated diffuse extracellular AGE-deposition as well as dense intracellular AGE-deposition in macrophage- and vascular smooth muscle cell (SMC)-derived foam cells. In vitro experiments using both CHO cells overexpressing macrophage scavenger receptor-A (MSR-A) and peritoneal macrophages from MSR-A-knockout mice have shown that the MSR-A plays a major role in endocytic uptake of AGE-proteins by macrophages. Furthermore, in vitro experiments with rabbit arterial SMCs demonstrated a novel AGE-receptor mediating endocytosis of AGE-proteins. These in vivo and in vitro experiments suggest that AGE-proteins formed extracellularly in atherosclerotic lesions are endocytosed by macrophages through MSR-A in the early stage, and by SMCs through the novel AGE-receptor in the advanced stage, implicating functional contribution of the AGE-receptor-mediated interaction of AGE-proteins with these cells to atherosclerotic processes in arterial walls.
Sano
H
H
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
Nagai
R
R
Matsumoto
K
K
Horiuchi
S
S
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells; D006224:Cricetinae; D004705:Endocytosis; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D011506:Proteins; D011956:Receptors, Cell Surface