Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease
Background: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61h/h) called ‘HypoE’ when fed an atherogenic, ‘Paigen’ diet develop occlusive, atherosclerotic coronary arterial disease (CHD), myocardial infarctions (MI), and heart...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Public Library of Science
2013
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| Online Access: | http://hdl.handle.net/1721.1/76336 https://orcid.org/0000-0003-4541-5181 |
| _version_ | 1826201458997985280 |
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| author | Nakagawa-Toyama, Yumiko Zhang, Songwen Krieger, Monty |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Nakagawa-Toyama, Yumiko Zhang, Songwen Krieger, Monty |
| author_sort | Nakagawa-Toyama, Yumiko |
| collection | MIT |
| description | Background:
Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61h/h) called ‘HypoE’ when fed an atherogenic, ‘Paigen’ diet develop occlusive, atherosclerotic coronary arterial disease (CHD), myocardial infarctions (MI), and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet). Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals.
Methodology/Principal Findings:
HypoE mice were maintained on a standard lab chow diet (control) until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western) or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented.
Conclusions/Significance:
HypoE mice provide a powerful, surgery-free, diet-‘titratable’ small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation) on a variety of features of cardiovascular disease. |
| first_indexed | 2024-09-23T11:52:09Z |
| format | Article |
| id | mit-1721.1/76336 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:52:09Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/763362022-10-01T06:34:27Z Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease Nakagawa-Toyama, Yumiko Zhang, Songwen Krieger, Monty Massachusetts Institute of Technology. Department of Biology Nakagawa-Toyama, Yumiko Zhang, Songwen Krieger, Monty Background: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61h/h) called ‘HypoE’ when fed an atherogenic, ‘Paigen’ diet develop occlusive, atherosclerotic coronary arterial disease (CHD), myocardial infarctions (MI), and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet). Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. Methodology/Principal Findings: HypoE mice were maintained on a standard lab chow diet (control) until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western) or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. Conclusions/Significance: HypoE mice provide a powerful, surgery-free, diet-‘titratable’ small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation) on a variety of features of cardiovascular disease. National Institutes of Health (U.S.) National Heart, Lung, and Blood Institute 2013-01-23T14:58:34Z 2013-01-23T14:58:34Z 2012-10 2012-04 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/76336 Nakagawa-Toyama, Yumiko, Songwen Zhang, and Monty Krieger. “Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease.” Ed. Massimo Federici. PLoS ONE 7.10 (2012): e47965. Web. https://orcid.org/0000-0003-4541-5181 en_US http://dx.doi.org/10.1371/journal.pone.0047965 PLoS One Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Nakagawa-Toyama, Yumiko Zhang, Songwen Krieger, Monty Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease |
| title | Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease |
| title_full | Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease |
| title_fullStr | Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease |
| title_full_unstemmed | Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease |
| title_short | Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease |
| title_sort | dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease |
| url | http://hdl.handle.net/1721.1/76336 https://orcid.org/0000-0003-4541-5181 |
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