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Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice

We assessed the effects of the sacubitril/valsartan combination drug (LCZ696), in comparison to valsartan alone, on the progression of atherosclerotic plaque formation and inflammatory gene expression in apolipoprotein E- deficient mice (apoE(−/−) mice). Seventy-two apoE(−/−) mice were fed a western...

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Autores principales: Zhang, Hui, Liu, Gangqiong, Zhou, Wenping, Zhang, Wenjing, Wang, Kai, Zhang, Jinying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482143/
https://www.ncbi.nlm.nih.gov/pubmed/31019233
http://dx.doi.org/10.1038/s41598-019-42994-1
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author Zhang, Hui
Liu, Gangqiong
Zhou, Wenping
Zhang, Wenjing
Wang, Kai
Zhang, Jinying
author_facet Zhang, Hui
Liu, Gangqiong
Zhou, Wenping
Zhang, Wenjing
Wang, Kai
Zhang, Jinying
author_sort Zhang, Hui
collection PubMed
description We assessed the effects of the sacubitril/valsartan combination drug (LCZ696), in comparison to valsartan alone, on the progression of atherosclerotic plaque formation and inflammatory gene expression in apolipoprotein E- deficient mice (apoE(−/−) mice). Seventy-two apoE(−/−) mice were fed a western diet and a constrictive silastic tube was used to elicit carotid lesion formation. The animals were separated into a control group, a valsartan group or an LCZ696 group (n = 24 in each group). Plaques in the carotid artery were harvested 12 weeks later for histological examination. The levels of pro-inflammatory genes in the plasma and lesions were detected using real-time PCR and ELISA. Valsartan or LCZ696 treatment remarkably inhibited the expression of pro-inflammatory genes, including interleukin-6, matrix metalloproteinase-8 and monocyte chemotactic protein-1, in comparison with the control group. Meanwhile, both valsartan and LCZ696 suppressed the formation of atherosclerotic plaques by decreasing plaque lipid content and cross-sectional plaque area and increasing the content of plaque collagen and fibrous cap thickness. In particular, LCZ696 performed the best in suppressing atherosclerosis and inhibiting the level of pro-inflammatory genes. LCZ696 significantly ameliorated atherosclerosis and inflammation in apoE(−/−) mice compared with valsartan.
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spelling pubmed-64821432019-05-03 Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice Zhang, Hui Liu, Gangqiong Zhou, Wenping Zhang, Wenjing Wang, Kai Zhang, Jinying Sci Rep Article We assessed the effects of the sacubitril/valsartan combination drug (LCZ696), in comparison to valsartan alone, on the progression of atherosclerotic plaque formation and inflammatory gene expression in apolipoprotein E- deficient mice (apoE(−/−) mice). Seventy-two apoE(−/−) mice were fed a western diet and a constrictive silastic tube was used to elicit carotid lesion formation. The animals were separated into a control group, a valsartan group or an LCZ696 group (n = 24 in each group). Plaques in the carotid artery were harvested 12 weeks later for histological examination. The levels of pro-inflammatory genes in the plasma and lesions were detected using real-time PCR and ELISA. Valsartan or LCZ696 treatment remarkably inhibited the expression of pro-inflammatory genes, including interleukin-6, matrix metalloproteinase-8 and monocyte chemotactic protein-1, in comparison with the control group. Meanwhile, both valsartan and LCZ696 suppressed the formation of atherosclerotic plaques by decreasing plaque lipid content and cross-sectional plaque area and increasing the content of plaque collagen and fibrous cap thickness. In particular, LCZ696 performed the best in suppressing atherosclerosis and inhibiting the level of pro-inflammatory genes. LCZ696 significantly ameliorated atherosclerosis and inflammation in apoE(−/−) mice compared with valsartan. Nature Publishing Group UK 2019-04-24 /pmc/articles/PMC6482143/ /pubmed/31019233 http://dx.doi.org/10.1038/s41598-019-42994-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Hui
Liu, Gangqiong
Zhou, Wenping
Zhang, Wenjing
Wang, Kai
Zhang, Jinying
Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice
title Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice
title_full Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice
title_fullStr Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice
title_full_unstemmed Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice
title_short Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice
title_sort neprilysin inhibitor–angiotensin ii receptor blocker combination therapy (sacubitril/valsartan) suppresses atherosclerotic plaque formation and inhibits inflammation in apolipoprotein e- deficient mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482143/
https://www.ncbi.nlm.nih.gov/pubmed/31019233
http://dx.doi.org/10.1038/s41598-019-42994-1
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