Artikel
End Organ Damage in Transgenic Rats with Ang II-Dependent Hypertension Involves Local Formation of Advanced Glycation End Products (AGEs)
Die Rolle von glykierten Proteinen (AGEs) für die Entstehung von Ang II-abhängigen Endorganschäden
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Autoren
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J. Bohlender
- Klinik für Innere Medizin III (Jena, D)
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S. Franke
- Klinik für Innere Medizin III (Jena, D)
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G. Stein
- Klinik für Innere Medizin III (Jena, D)
| Veröffentlicht: | 11. November 2004 |
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Gliederung
Text
Aims
Advanced glycation end products (AGEs) have been associated with chronic renal insufficiency and cytokine-mediated proinflammatory states. AGEs may produce protein crosslinks with tissue stiffening and induce receptor-mediated proinflammatory responses with cellular dysfunction. Their role in angiotensin-induced glomerular and vascular damage, however, remains unclear.
Methods
We examined kidneys, hearts, and aortas from rats, double transgenic for human angiotensinogen and renin (TGR) aged 3 months and nontransgenic controls (CTR) by immuno-histochemical staining for N-omega-(carboxymehtyl)-lysine (CML), NFkappaB. CML and pentosidine-modified proteins in plasma were measured by ELISA and HPLC (n=8 per group). Blood pressure was measured by tail-cuff.
Results
Systolic blood pressure was >180 mm Hg in TGR and 115-130 mm Hg in CTR. TGR showed avid staining for CML in glomeruli while glomerular and interstitial inflammatory damage and fibrosis was detected. NFkappaB was locally activated. Collecting duct epithe-lium, endothelium of renal and coronary arteries similarly showed CMl staining. Aortic walls showed a weaker patchy staining of the smooth muscle cell layers and interstitial matrix respetively. Adjacent tissue did not stain for CML nor did tissues from CTR. Plasma CML was about 15% higher in TGR vs. CTR (p<0.05), whereas pentosidine concentrations were below the assay sensitivity in both TGR and CTR.
Conclusion
We here demonstrate for the first time local formation and accumulation of AGEs in glomeruli and arteries in rats with transgenic, angiotensin-induced hypertension and endorgan damage. The AGEs may induce local inflammation by activation of RAGE, their receptor, and NFkappaB-dependent intracellular pathways thereby promoting glomerular and vascular damage and fibrosis.
