Artery Research

Volume 7, Issue 3-4, September 2013, Pages 141 - 141

P4.21 MILD UREMIA INDUCES AORTIC DILATATION AND HEART REMODELLING VIA NF-KB ACTIVATION

Authors
E. Kaschina1, A. Akohov1, M. Sommerfeld1, B. Iliev2, H. Peters2, T. Unger3, S. Kraemer2
1Center for Cardiovascular Research, Institute of Pharmacology, Charité Universitätsmedizin Berlin, Berlin, Germany
2Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany
3CARIM - School for Cardiovascular Diseases Maastricht University, Maastricht, Netherlands
Available Online 11 November 2013.
DOI
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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Journal
Artery Research
Volume-Issue
7 - 3-4
Pages
141 - 141
Publication Date
2013/11/11
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2013.10.139How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

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  -