Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse
Abstract
The db/db mouse is a well-established model of diabetes. Previous reports have documented contractile dysfunction (i.e., cardiomyopathy) in these animals, although the extant literature provides limited insights into cardiac structure and function as they change over time. To better elucidate the natural history of cardiomyopathy in db/db mice, we performed cardiac magnetic resonance (CMR) scans on these animals. CMR imaging was conducted with a 4.7-T magnet on female db/db mice and control db/+ littermates at 5, 9, 13, 17, and 22 wk of age. Gated gradient echo sequences were used to obtain cineographic short-axis slices from apex to base. From these images left ventricular (LV) mass (LVM), wall thickness, end-diastolic volume (LVEDV), and ejection fraction (LVEF) were determined. Additionally, cardiac [18 F]fluorodeoxyglucose ([18 F]FDG) PET scanning, pressure-volume loops, and real-time quantitative PCR on db/db myocardium were performed. Relative to control, db/db mice developed significant increases in LVM and wall thickness as early as 9 wk of age. LVEDV diverged slightly later, at 13 wk. Interestingly, compared with the baseline level, LVEF in the db/db group did not decrease significantly until 22 wk. Additionally, [18 F]FDG metabolic imaging showed a 40% decrease in glucose uptake in db/db mice. Furthermore, contractile dysfunction was observed in 15-wk db/db mice undergoing pressure-volume loops. Finally, real-time quantitative PCR revealed an age-dependent recapitulation of the fetal gene program, consistent with a myopathic process. In summary, as assessed by CMR, db/db mice develop characteristic structural and functional changes consistent with cardiomyopathy.
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In animal models of obesity, most in vivo studies reveal mildly impaired systolic function that is absent in younger animals (<12 wk of age) but becomes evident between 12 and 20 wk of age.
“Generally, most studies reveal evidence of mildly impaired systolic function in vivo that is absent in younger animals (<12 wk of age) but become evident between 12 and 20 wk of age (34, 53, 313, 357, 361, 388).”
From Cardiac remodeling in obesity (2008) · cites this paper as [388]
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- Authors
- Yue, P., Arai, T., Terashima, M., Sheikh, A. Y., Cao, F., Charo, D., Hoyt, G., Robbins, R. C., Ashley, E. A., Wu, J., Yang, P. C., & Tsao, P. S.
- Affiliations
- Stanford Medicine (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2007-05
- Volume
- 292
- Issue
- 5
- Pages
- H2106-H2118
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2127757197
- Cited by
- 81
- References
- 97
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 2 · 2012: 5
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (5k23eb002063-05)
- U.S. Public Health Service (1401 DZK 071333)
- National Heart, Lung, and Blood Institute (F32HL078108)
- National Institute of Biomedical Imaging and Bioengineering (5K23 EB 002063)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- db/db mice, type 2 diabetes, diabetic cardiomyopathy, cardiac magnetic resonance, left ventricular hypertrophy, ejection fraction, myocardial glucose uptake, fetal gene program, contractile dysfunction, pressure-volume loops
- MeSH terms
- Animals, Female, Heart Ventricles, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Mice, Inbred Strains, Cardiomyopathies, Ventricular Dysfunction, Left, Mice
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