title: [AGE-RAGE: a hypothesis or a mechanism?].
abstract: Acausal relation between hyperglycemia and accelerated atherosclerosis has been recently suggested. The AGE-RAGE interaction is a potential mechanism underlying the accelerated atherosclerosis. Hyperglycemia causes via nonenzymatic glycation the formation of AGEs (advanced glycation endproducts). AGEs as well as other ligands like S100/Calgranulin and Amphoterin mediate receptor-independent and -dependent (via the interaction with RAGE) effects. The ligand-RAGE-interaction results in an activation of NF-kappaB, increased expression of cytokines, chemokines, and adhesion molecules and induces oxidative stress. A relevant role of the ligand-RAGE-interaction has been demonstrated in in vivo studies, both for the accelerated atherosclerosis and increased neointima formation in diabetes mellitus. Recent data analysing atherosclerotic lesions of diabetic patients provide further evidence for the pathogenetic role of the RAGE-ligand-interaction. In addition, new experimental data established that AGEs interact with other receptors than RAGE, while RAGE interacts with a diverse group of ligands. Thus, further studies are needed for the characterization of the ligand-RAGE-interaction. These studies will provide a rationale for the development of new therapeutic approaches for accelerated atherosclerosis in diabetes mellitus.
authors.affiliation: Abteilung Endokrinologie und Stoffwechsel, Universitätsklinik Heidelberg, Heidelberg. berend.isermann@med.uni-heidelberg.de
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.forename: Per M
authors.initials: PM
authors.lastname: Humpert
authors.forename: Gottfried
authors.initials: G
authors.lastname: Rudofsky
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Robert
authors.initials: R
authors.lastname: Ritzel
authors.forename: Thoralf
authors.initials: T
authors.lastname: Wendt
authors.forename: Michael
authors.initials: M
authors.lastname: Morcos
authors.forename: Christian
authors.initials: C
authors.lastname: Kasperk
authors.forename: Andreas
authors.initials: A
authors.lastname: Hamann
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D017127:Glycation End Products, Advanced / Q000276:immunology*; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D018448:Models, Immunological; D018384:Oxidative Stress / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D016207:Cytokines; D017127:Glycation End Products, Advanced