Abstract 18850: Multiparametric MRI Detects Early Biomarkers of Cardiomyopathy in C57Bl/6 Mice Fed a High-fat Diet
Introduction: Obesity and diabetes can lead to cardiomyopathy and heart failure even in the absence of obstructive coronary artery disease (CAD). Mechanisms underlying these disease processes are incompletely understood. Mice fed a high fat diet (HFD) for 8-16 months do not develop CAD, but do recapitulate many aspects of human diabetic cardiomyopathy. We used cardiac MRI to establish earlier biomarkers of cardiomyopathy in HFD mice.
Methods: Wild type C57Bl/6 mice (control) on a low-fat diet (n = 9) and C57Bl/6 mice on a HFD (n = 9) were imaged at 6, 12 and 18 weeks after start of diet. The MRI protocol included quantitative first-pass perfusion MRI at rest and at vasodilation with Regadenoson (0.1 μg/g body weight), cine imaging to measure LV volumes, LV mass, and LV wall thickness, and cine DENSE MRI to measure myocardial strain. Glucose tolerance was also evaluated in the two groups of mice.
Results: Body weight was increased in HFD mice (Figure A, *p<0.05 vs. control at the same timepoint, #p<0.05 vs. HFD at 6 wks, $p<0.05 vs. HFD at 12 wks, $$p<0.05 vs. control at 6wks). The HFD mice were glucose intolerant starting at 6 wks of diet. Stress perfusion was reduced in HFD vs. control mice at 18 wks after start of diet (Figure B, p<0.05), whereas rest perfusion was similar to controls. End-diastolic (ED) and end-systolic (ES) wall thickness were increased in the HFD mice after 18 wks of diet (Figure C, *p<0.05 vs. control at 18 wks, #p<0.05 vs. HFD at 6 and 12 wks). Also, LV mass was increased in HFD mice at 18 weeks post-diet (Figure D, *p<0.05 vs. control at 18 wks, #p<vs. HFD at 6 and 12 wks). There were no significant differences in myocardial strain between the two groups.
Conclusions: At 18 wks of HFD, multiparametric MRI detects LV hypertrophy and an impairment in stress perfusion, both hallmarks of human diabetic cardiomypothy. MRI applied to the HFD mouse model may be used in future studies to investigate underlying molecular mechanisms and therapies for cardiomyopathy due to obesity and diabetes.
Author Disclosures: N.K. Naresh: None. X. Chen: None. R.J. Roy: None. B.H. Annex: None. F.H. Epstein: None.
- © 2014 by American Heart Association, Inc.