Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106407
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Type: Journal article
Title: Modulation of the sympathetic nervous system by renal denervation prevents reduction of aortic distensibility in atherosclerosis prone ApoE-deficient rats
Author: Hohl, M.
Linz, D.
Fries, P.
Mueller, A.
Stroeder, J.
Urban, D.
Speer, T.
Geisel, J.
Hummel, B.
Laufs, U.
Schirmer, S.
Boehm, M.
Mahfoud, F.
Citation: Journal of Translational Medicine, 2016; 14(1):167-1-167-11
Publisher: BioMed Central
Issue Date: 2016
ISSN: 1479-5876
1479-5876
Statement of
Responsibility: 
Mathias Hohl, Dominik Linz, Peter Fries, Andreas Müller, Jonas Stroeder, Daniel Urban, Thimoteus Speer, Jürgen Geisel, Björn Hummel, Ulrich Laufs, Stephan H. Schirmer, Michael Böhm and Felix Mahfoud
Abstract: Background: Apolipoprotein E-deficient (ApoE−/−) rodents spontaneously develop severe hypercholesterolemia and increased aortic stiffness, both accepted risk factors for cardiovascular morbidity and mortality in humans. In patients with resistant hypertension renal denervation (RDN) may improve arterial stiffness, however the underlying mechanisms are incompletely understood. This study investigates the impact of RDN on aortic compliance in a novel atherosclerosis prone ApoE−/−-rat model. Methods: Normotensive, 8 weeks old ApoE−/− and Sprague–Dawley (SD) rats were subjected to bilateral surgical RDN (n = 6 per group) or sham operation (n = 5 per group) and fed with normal chow for 8 weeks. Compliance of the ascending aorta was assessed by magnetic resonance imaging. Vasomotor function was measured by aortic ring tension recordings. Aortic collagen content was quantified histologically and plasma aldosterone levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: After 8 weeks, ApoE−/−-sham demonstrated a 58 % decrease in aortic distensibility when compared with SD-sham (0.0051 ± 0.0011 vs. 0.0126 ± 0.0023 1/mmHg; p = 0.02). This was accompanied by an impaired endothelium-dependent relaxation of aortic rings and an increase in aortic medial fibrosis (17.87 ± 1.4 vs. 12.27 ± 1.1 %; p = 0.006). In ApoE−/−-rats, RDN prevented the reduction of aortic distensibility (0.0128 ± 0.002 vs. 0.0051 ± 0.0011 1/mmHg; p = 0.01), attenuated endothelial dysfunction, and decreased aortic medial collagen content (12.71 ± 1.3 vs. 17.87 ± 1.4 %; p = 0.01) as well as plasma aldosterone levels (136.33 ± 6.6 vs. 75.52 ± 8.4 pg/ml; p = 0.0003). Cardiac function and metabolic parameters such as hypercholesterolemia were not influenced by RDN. Conclusion: ApoE−/−-rats spontaneously develop impaired vascular compliance. RDN improves aortic distensibility and attenuated endothelial dysfunction in ApoE−/−-rats. This was associated with a reduction in aortic fibrosis formation, and plasma aldosterone levels.
Keywords: ApoE-deficient rats; hypercholesterolemia; Aortic distensibility; renal sympathetic denervation
Rights: © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030067418
DOI: 10.1186/s12967-016-0914-9
Appears in Collections:Medicine publications

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