Cardiovascular magnetic resonance detects the progression of impaired myocardial perfusion reserve and increased left-ventricular mass in mice fed a high-fat diet

Journal of Cardiovascular Magnetic Resonance

Research

Christopher M. Kramer¹  Xiao Chen²  Nivedita K. Naresh²  Brian H. Annex³  Frederick H. Epstein⁴  Li-Ming Gan⁵  Robert J. Lye⁶  Joshua T. Butcher⁷  Brant E. Isakson⁷ 

[1] Cardiovascular Medicine, University of Virginia, Charlottesville, VA, USA;Department of Radiology, University of Virginia, Charlottesville, VA, USA;Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA;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;Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA;Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA;Department of Radiology, University of Virginia, Charlottesville, VA, USA;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;Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA;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;

关键词: Myocardial perfusion reserve;    Mouse;    Cardiovascular magnetic resonance;    Obesity;    Type 2 diabetes mellitus;   

DOI  :  10.1186/s12968-016-0273-y

 received in 2016-05-04, accepted in 2016-08-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundImpaired 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.MethodsC57Bl/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.ResultsBody 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.ConclusionsC57Bl/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.

【 授权许可】

CC BY   
© The Author(s). 2016