P4.21 MILD UREMIA INDUCES AORTIC DILATATION AND HEART REMODELLING VIA NF-KB ACTIVATION
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- 10.1016/j.artres.2013.10.139How to use a DOI?
- Abstract
Objectives: The aim of this study was to investigate the effects of mild uremia on aortic and heart remodelling in the rat.
Methods: Mild uremia was induced by reduction of renal mass after 5/6 nephrectomy (NE). Rats with proteinuria >300 mg/24h were included in further investigations. Four weeks after NE, an abdominal aortic aneurysm (AAA) was induced via continuous infusion of an isolated aortic segment with elastase. One group of NE animals was additionally treated with hydralazine (15 mg/kg). Sham operated rats served as controls (n=12). Aortic diameter and heart function were measured by ultrasound biomicroscopy. Aortic tissues, renal functional parameters and serum pro-inflammatory cytokines were investigated.
Results: Uremia induced aortic dilatation (2.1±0.04mm vs. 1.8±0.03mm, p<0.001). Histological analysis revealed an outward aortic remodelling, increased elastin fragmentation (p<0.05), cystic medial degradation, calcification of tunica media and inflammatory infiltrates in the adventitia. After aneurysm induction, aortic diameter was further increased in the NE group as compared to AAA rats without NE (2.6±0.05mm vs 2.3±0.03mm, p<0.05). Hydralazine treatment significantly reduced blood pressure (115±4 vs 160±7mmHg, p<0.05) but did not influence aortic diameter. Protein expression of NF-kB was strongly (3-fold) up-regulated in aortic tissues from NE rats. MMP2, MMP9, cathepsin D and TGF-beta1 were significantly (p<0.05) increased after AAA and further up-regulated in the NE/AAA group. Uremia decreased systolic heart function (p<0.05).
Conclusion: Mild uremia induces aortic dilation and heart remodelling independently of blood pressure elevation. Activation of NFkB by uremic toxins may contribute to remodelling via inhibition of elastin- and collagen gene transcription.
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TY - JOUR AU - E. Kaschina AU - A. Akohov AU - M. Sommerfeld AU - B. Iliev AU - H. Peters AU - T. Unger AU - S. Kraemer PY - 2013 DA - 2013/11/11 TI - P4.21 MILD UREMIA INDUCES AORTIC DILATATION AND HEART REMODELLING VIA NF-KB ACTIVATION JO - Artery Research SP - 141 EP - 141 VL - 7 IS - 3-4 SN - 1876-4401 UR - https://doi.org/10.1016/j.artres.2013.10.139 DO - 10.1016/j.artres.2013.10.139 ID - Kaschina2013 ER -