Advanced glycation end products: a possible link to angiotensin in an animal model.
Advanced glycation end products (AGEs) have been associated with progressive vascular and renal damage in a variety of pathological conditions such as renal failure and diabetes mellitus. The formation of AGEs is generally attributed to increased oxidative and carbonyl stress or hyperglycemia. Activation of the cellular receptor of AGE (RAGE) leads to subsequent cellular activation and proinflammatory responses. Angiotensin (Ang) produces cellular oxidative stress and similarly promotes end organ damage via its type 1 receptor. We investigated the interrelation between these two systems in a new transgenic rat (TGR) model with Ang II-dependent hypertension and renal damage and in nontransgenic controls. TGR showed increased systolic blood pressure (approximately 210 mmHg), proteinuria, and increased renal collagen I mRNA expression compared with normotensive nontransgenic controls. Immunohistochemical staining of kidney sections showed colocalization for Nepsilon-carboxy(methyl)lysine, RAGE, and NF-kappaB in TGR glomeruli. These features were absent in nontransgenic controls. Our observations suggest a possible link between Ang II-dependent end-organ damage and the AGE/RAGE axis in vivo. TGRs provide an excellent model to study the interrelation between the renin-angiotensin system and the AGE/RAGE axis in promoting cardiovascular end-organ damage, which would otherwise not be possible in humans.
Bohlender
Jürgen
J
Klinik für Innere Medizin III, Friedrich-Schiller University, Erlanger Allee 101, D-07740 Jena, Germany. j.bohlender@uni-jena.de
Franke
Sybille
S
Sommer
Manfred
M
Stein
Günter
G
D000808:Angiotensinogen / Q000172:deficiency / Q000235:genetics; D000809:Angiotensins / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D023421:Models, Animal; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D012083:Renin / Q000172:deficiency / Q000235:genetics
D000809:Angiotensins; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000808:Angiotensinogen; D012083:Renin