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Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs
Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of fa...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215431/ https://www.ncbi.nlm.nih.gov/pubmed/30305304 http://dx.doi.org/10.1242/dmm.036632 |
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author | Fang, Bin Ren, Xueyang Wang, Ying Li, Ze Zhao, Lihua Zhang, Manling Li, Chu Zhang, Zhengwei Chen, Lei Li, Xiaoxue Liu, Jiying Xiong, Qiang Zhang, Lining Jin, Yong Liu, Xiaorui Li, Lin Wei, Hong Yang, Haiyuan Li, Rongfeng Dai, Yifan |
author_facet | Fang, Bin Ren, Xueyang Wang, Ying Li, Ze Zhao, Lihua Zhang, Manling Li, Chu Zhang, Zhengwei Chen, Lei Li, Xiaoxue Liu, Jiying Xiong, Qiang Zhang, Lining Jin, Yong Liu, Xiaorui Li, Lin Wei, Hong Yang, Haiyuan Li, Rongfeng Dai, Yifan |
author_sort | Fang, Bin |
collection | PubMed |
description | Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of familial hypercholesterolemia and atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 system (CRISPR/Cas9) was used to disrupt the ApoE gene in Bama miniature pigs. Biallelic-modified ApoE pigs with in-frame mutations (ApoE(m/m)) and frameshift mutations (ApoE(−/−)) were simultaneously produced. ApoE(−/−) pigs exhibited moderately increased plasma cholesterol levels when fed with a regular chow diet, but displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries after feeding on a high-fat and high-cholesterol (HFHC) diet for 6 months. Thus, these ApoE(−/−) pigs could be valuable large animal models for providing further insight into translational studies of atherosclerosis. |
format | Online Article Text |
id | pubmed-6215431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-62154312018-11-05 Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs Fang, Bin Ren, Xueyang Wang, Ying Li, Ze Zhao, Lihua Zhang, Manling Li, Chu Zhang, Zhengwei Chen, Lei Li, Xiaoxue Liu, Jiying Xiong, Qiang Zhang, Lining Jin, Yong Liu, Xiaorui Li, Lin Wei, Hong Yang, Haiyuan Li, Rongfeng Dai, Yifan Dis Model Mech Resource Article Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of familial hypercholesterolemia and atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 system (CRISPR/Cas9) was used to disrupt the ApoE gene in Bama miniature pigs. Biallelic-modified ApoE pigs with in-frame mutations (ApoE(m/m)) and frameshift mutations (ApoE(−/−)) were simultaneously produced. ApoE(−/−) pigs exhibited moderately increased plasma cholesterol levels when fed with a regular chow diet, but displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries after feeding on a high-fat and high-cholesterol (HFHC) diet for 6 months. Thus, these ApoE(−/−) pigs could be valuable large animal models for providing further insight into translational studies of atherosclerosis. The Company of Biologists Ltd 2018-10-01 2018-10-10 /pmc/articles/PMC6215431/ /pubmed/30305304 http://dx.doi.org/10.1242/dmm.036632 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Resource Article Fang, Bin Ren, Xueyang Wang, Ying Li, Ze Zhao, Lihua Zhang, Manling Li, Chu Zhang, Zhengwei Chen, Lei Li, Xiaoxue Liu, Jiying Xiong, Qiang Zhang, Lining Jin, Yong Liu, Xiaorui Li, Lin Wei, Hong Yang, Haiyuan Li, Rongfeng Dai, Yifan Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs |
title | Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs |
title_full | Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs |
title_fullStr | Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs |
title_full_unstemmed | Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs |
title_short | Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs |
title_sort | apolipoprotein e deficiency accelerates atherosclerosis development in miniature pigs |
topic | Resource Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215431/ https://www.ncbi.nlm.nih.gov/pubmed/30305304 http://dx.doi.org/10.1242/dmm.036632 |
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