Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet.
BACKGROUND: Mice deficient in the LDL receptor (Ldlr(-/-) mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to d...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3338468?pdf=render |
| _version_ | 1818290045718626304 |
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| author | Yanling Ma Wenyi Wang Jie Zhang Youli Lu Wenyu Wu Hong Yan Yiping Wang |
| author_facet | Yanling Ma Wenyi Wang Jie Zhang Youli Lu Wenyu Wu Hong Yan Yiping Wang |
| author_sort | Yanling Ma |
| collection | DOAJ |
| description | BACKGROUND: Mice deficient in the LDL receptor (Ldlr(-/-) mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr(-/-) mice. METHODOLOGY/PRINCIPAL FINDINGS: Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with the complication of obesity. CONCLUSIONS/SIGNIFICANCE: Ldlr-deficient mice on the HF diet tend to develop site-selective and size-specific atherosclerotic lesions over time. The current study should provide information on diet induction or drug intervention times and facilitate estimation of the appropriate locations of atherosclerotic lesions in Ldlr(-/-) mice. |
| first_indexed | 2024-12-13T02:21:56Z |
| format | Article |
| id | doaj.art-abc95d0aa5e3471093ba33f3c691a3bd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T02:21:56Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-abc95d0aa5e3471093ba33f3c691a3bd2022-12-22T00:02:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3583510.1371/journal.pone.0035835Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet.Yanling MaWenyi WangJie ZhangYouli LuWenyu WuHong YanYiping WangBACKGROUND: Mice deficient in the LDL receptor (Ldlr(-/-) mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr(-/-) mice. METHODOLOGY/PRINCIPAL FINDINGS: Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with the complication of obesity. CONCLUSIONS/SIGNIFICANCE: Ldlr-deficient mice on the HF diet tend to develop site-selective and size-specific atherosclerotic lesions over time. The current study should provide information on diet induction or drug intervention times and facilitate estimation of the appropriate locations of atherosclerotic lesions in Ldlr(-/-) mice.http://europepmc.org/articles/PMC3338468?pdf=render |
| spellingShingle | Yanling Ma Wenyi Wang Jie Zhang Youli Lu Wenyu Wu Hong Yan Yiping Wang Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. PLoS ONE |
| title | Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. |
| title_full | Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. |
| title_fullStr | Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. |
| title_full_unstemmed | Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. |
| title_short | Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet. |
| title_sort | hyperlipidemia and atherosclerotic lesion development in ldlr deficient mice on a long term high fat diet |
| url | http://europepmc.org/articles/PMC3338468?pdf=render |
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