Cardiovascular magnetic resonance detects the progression of impaired myocardial perfusion reserve and increased left-ventricular mass in mice fed a high-fat diet.
Impaired myocardial perfusion reserve (MPR) is prevalent in obesity and diabetes, even in the absence of obstructive coronary artery disease (CAD), and is prognostic of adverse events. We sought to establish the time course of reduced MPR and to investigate associated vascular and tissue properties in mice fed a high-fat diet (HFD), as they are an emerging model of human obesity, diabetes, and reduced MPR without obstructive CAD.



C57Bl/6 mice fed a HFD or a low-fat diet (control) were imaged at 6, 12, 18 and 24 weeks post-diet. The cardiovascular magnetic resonance (CMR) protocol included multi-slice cine imaging to assess ejection fraction (EF), left-ventricular (LV) mass, LV wall thickness (LVWT), and LV volumes, and first-pass perfusion CMR to quantify MPR. Coronary vascular reactivity, aortic atherosclerosis, myocardial capillary density and tissue fibrosis were also assessed.



Body weight was increased in HFD mice at 6-24 weeks post-diet (p < 0.05 vs. control). MPR in HFD mice was reduced and LV mass and LVWT were increased in HFD mice at 18 and 24 weeks post-diet (p < 0.05 vs. control). Coronary arteriolar vascular reactivity to adenosine and acetylcholine were reduced in HFD mice (p < 0.05 vs. control). There were no significant differences in cardiac volumes, EF, or capillary density measurements between the two groups. Histology showed interstitial fibrosis in HFD and no aortic atherosclerosis in either group.



C57Bl/6 mice fed a HFD for 18-24 weeks have progressively increased LV mass and impaired MPR with fibrosis, normal capillary density and no aortic plaque. These results establish C57Bl/6 mice fed a HFD for 18-24 weeks as a model of impaired MPR without obstructive CAD due to obesity and diabetes.
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Nivedita K
NK
Naresh
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.|Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.
Joshua T
JT
Butcher
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Robert J
RJ
Lye
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Xiao
X
Chen
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.|Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.
Brant E
BE
Isakson
Department of Molecular and Clinical Medicine, AstraZeneca R&D, Mölndal, Sweden.|Institute of Medicine, Sahlgrenska Academy, CVMD Early Clinical Development, AstraZeneca R&D, Mölndal, Sweden.
Li-Ming
LM
Gan
Cardiovascular Medicine, University of Virginia, Charlottesville, VA, USA.|Department of Radiology, University of Virginia, Charlottesville, VA, USA.
Christopher M
CM
Kramer
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.|Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.|Cardiovascular Medicine, University of Virginia, Charlottesville, VA, USA.
Brian H
BH
Annex
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. fhe6b@virginia.edu.|Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA. fhe6b@virginia.edu.|Department of Radiology, University of Virginia, Charlottesville, VA, USA. fhe6b@virginia.edu.
Frederick H
FH
Epstein
D000818:Animals; D003326:Coronary Circulation; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009765:Obesity / Q000150:complications*; D011237:Predictive Value of Tests; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
Cardiovascular magnetic resonance; Mouse; Myocardial perfusion reserve; Obesity; Type 2 diabetes mellitus