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Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis

BACKGROUND: Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E–deficient (ApoE(−/−)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. METHODS AND RESULTS: Male ApoE(−/−) mice underwent sham surgery (n=16) o...

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Autores principales: Pathak, Alokkumar S., Huang, Jianhua, Rojas, Mauricio, Bazemore, Taylor C., Zhou, Ruihai, Stouffer, George A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859283/
https://www.ncbi.nlm.nih.gov/pubmed/27039929
http://dx.doi.org/10.1161/JAHA.115.002953
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author Pathak, Alokkumar S.
Huang, Jianhua
Rojas, Mauricio
Bazemore, Taylor C.
Zhou, Ruihai
Stouffer, George A.
author_facet Pathak, Alokkumar S.
Huang, Jianhua
Rojas, Mauricio
Bazemore, Taylor C.
Zhou, Ruihai
Stouffer, George A.
author_sort Pathak, Alokkumar S.
collection PubMed
description BACKGROUND: Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E–deficient (ApoE(−/−)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. METHODS AND RESULTS: Male ApoE(−/−) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P<0.05) and descending thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8]; P<0.05), compared to sham surgery. There was an increased amount of aortic arch lipid staining in the D8LR group (22.7% [22.1, 32.7]), compared to sham‐surgery, but less than observed with chronic RAS. Lipid staining in the aortic arch was not increased in the D4LR group, and lipid staining in the descending aorta was not increased in either the D8LR or D4LR groups. There was less macrophage expression in infrarenal aortic atheroma in the D4LR and D8LR groups compared to the chronic RAS group. CONCLUSIONS: Restoration of renal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation.
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spelling pubmed-48592832016-05-20 Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis Pathak, Alokkumar S. Huang, Jianhua Rojas, Mauricio Bazemore, Taylor C. Zhou, Ruihai Stouffer, George A. J Am Heart Assoc Original Research BACKGROUND: Chronic unilateral renal artery stenosis (RAS) causes accelerated atherosclerosis in apolipoprotein E–deficient (ApoE(−/−)) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown. METHODS AND RESULTS: Male ApoE(−/−) mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4LR; n=6), 8 days later (D8LR; n=11), or left in place for 90 days (chronic RAS; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin II levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic RAS resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P<0.05) and descending thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8]; P<0.05), compared to sham surgery. There was an increased amount of aortic arch lipid staining in the D8LR group (22.7% [22.1, 32.7]), compared to sham‐surgery, but less than observed with chronic RAS. Lipid staining in the aortic arch was not increased in the D4LR group, and lipid staining in the descending aorta was not increased in either the D8LR or D4LR groups. There was less macrophage expression in infrarenal aortic atheroma in the D4LR and D8LR groups compared to the chronic RAS group. CONCLUSIONS: Restoration of renal blood flow at either 4 or 8 days after unilateral RAS had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation. John Wiley and Sons Inc. 2016-04-03 /pmc/articles/PMC4859283/ /pubmed/27039929 http://dx.doi.org/10.1161/JAHA.115.002953 Text en © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Pathak, Alokkumar S.
Huang, Jianhua
Rojas, Mauricio
Bazemore, Taylor C.
Zhou, Ruihai
Stouffer, George A.
Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis
title Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis
title_full Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis
title_fullStr Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis
title_full_unstemmed Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis
title_short Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE(−/−) Mice With Unilateral Renal Artery Stenosis
title_sort effects of restoration of blood flow on the development of aortic atherosclerosis in apoe(−/−) mice with unilateral renal artery stenosis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859283/
https://www.ncbi.nlm.nih.gov/pubmed/27039929
http://dx.doi.org/10.1161/JAHA.115.002953
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