Advanced glycation end products and receptor for advanced glycation end products in AA amyloidosis.
Advanced glycation end products (AGEs) may be involved in either amyloidogenesis or complications related to amyloid. We hypothesized that AGEs may influence the pathogenesis of AA amyloidosis, and investigated the spatial and temporal relationship between AGEs, carboxy methyl lysine (CML), the AGE receptor (RAGE), and AA amyloid in humans and mice. Specimens from patients with AL and ATTR amyloidosis served as a control. Using immunohistochemistry, AGEs, CML, and RAGE were found within amyloid deposits, more commonly in AA amyloid than in AL amyloid and not in ATTR amyloid. Western blotting showed that multiple proteins (between 12 and >60 kd) are modified, but not the AA amyloid fibril protein itself. In the murine model of AA amyloidosis, we found a marked interindividual variability with respect to local and systemic CML levels, as well as to splenic RAGE transcription. Serum levels of CML correlated with the duration of the inflammatory response but not with amounts of splenic RAGE mRNA. Other as yet unidentified variables, especially of the heterogeneous group of AGEs, probably modulate transcription of RAGE and influence amyloidogenesis. CML serum levels, in turn, may prove useful in predicting patients at risk.
Röcken
Christoph
C
Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany. christoph.roecken@medizin.uni-magdeburg.de
Kientsch-Engel
Rosemarie
R
Mansfeld
Sophie
S
Stix
Barbara
B
Stubenrauch
Kay
K
Weigle
Bernd
B
Bühling
Frank
F
Schwan
Mona
M
Saeger
Wolfgang
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein
D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000685:Serum Amyloid A Protein