Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease

Nakagawa-Toyama, Yumiko; Zhang, Songwen; Krieger, Monty

doi:10.1371/journal.pone.0047965

Cited by 22Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease

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Nakagawa-Toyama, Yumiko, Zhang, Songwen, Krieger, Monty·2012·PLoS ONE

DOI 10.1371/journal.pone.0047965PMC PMC3480446

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Abstract

BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/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.

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In controlled laboratory settings, social contact is linked to longer lifespan across many social species, including insects, rodents, and primates.
“Even in controlled laboratory environments (where external threats to survival are absent), the presence of social contact is associated with increased lifespan across a range of social species including honeybees, ants, Drosophila melanogaster22,23, mice24,25, and rats26–28, as well as in free-ranging groups of macaques29, and baboons30.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [25]

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Authors: Nakagawa-Toyama, Y., Zhang, S., & Krieger, M.
Affiliations: Massachusetts Institute of Technology (US)
Corresponding author: Krieger, Monty
ORCID: Krieger, Monty
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2012-10-24
Volume: 7
Issue: 10
Pages: e47965
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0047965
PMC: PMC3480446
OpenAlex: W2117829554
Cited by: 22
References: 42
Citations by year: 2024: 4 · 2023: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 3
FWCI: 2.61
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Figshare (submittedVersion, cc-by)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords: coronary artery disease, apolipoprotein E, atherogenic diet, cholate, social isolation, myocardial infarction, heart failure, hypercholesterolemia, disease progression, serum cholesterol, cardiomegaly, survival, mouse model
MeSH terms: Animals, Apolipoproteins E, Cholesterol, Coronary Disease, Diet, Atherogenic, Female, Humans, Hypercholesterolemia, Lipids, Lipoproteins, Male, Myocardium, Organ Size, Social Isolation, Survival Analysis, Disease Progression, Mice

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Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease

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