[AGE-RAGE: a hypothesis or a mechanism?].
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.
Isermann
Berend
B
Abteilung Endokrinologie und Stoffwechsel, Universitätsklinik Heidelberg, Heidelberg. berend.isermann@med.uni-heidelberg.de
Bierhaus
Angelika
A
Humpert
Per M
PM
Rudofsky
Gottfried
G
Chavakis
Triantafyllos
T
Ritzel
Robert
R
Wendt
Thoralf
T
Morcos
Michael
M
Kasperk
Christian
C
Hamann
Andreas
A
Nawroth
Peter P
PP
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*
D016207:Cytokines; D017127:Glycation End Products, Advanced