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Published on: February 14, 2025
Comprehensive MRI for the detection of subtle alterations in diastolic cardiac function in apoE/LDLR(-/-) mice with
Urszula Tyrankiewicz1, Tomasz Skorka1, Anna Orzylowska1
1Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, Poland.
Insights
ApoE/LDLR(-/-) mice with advanced atherosclerosis show preserved cardiac performance. Subtle diastolic alterations were detected using MRI, suggesting potential ischemic effects despite severe coronary artery disease.
Area of Science:
- Cardiovascular Research
- Medical Imaging
- Animal Models
Background:
- Atherosclerosis is a significant cardiovascular disease.
- ApoE/LDLR(-/-) mice are a common model for studying atherosclerosis.
- Cardiac function in this mouse model requires further characterization.
Purpose of the Study:
- To assess cardiac performance in vivo in ApoE/LDLR(-/-) mice with advanced atherosclerosis using MRI.
- To compare cardiac function between atherosclerotic ApoE/LDLR(-/-) mice and control C57BL/6J mice.
- To identify potential cardiac impairments associated with severe coronary atherosclerosis.
Main Methods:
- Utilized highly time-resolved cine-MRI and MR tagging for comprehensive cardiac assessment.
- Analyzed global and regional left ventricular (LV) function, including volumes, kinetics, strains, and rotations.
- Performed histological analysis with OMSB and ORO staining to confirm coronary atherosclerosis.
Main Results:
- MR-tagging revealed increased radial and circumferential systolic stretch and radial post-systolic strain index in ApoE/LDLR(-/-) mice.
- A decreased LV untwisting rate was observed in atherosclerotic mice compared to controls.
- Most cine-MRI parameters and global LV function remained unchanged, with only subtle diastolic alterations noted.
Conclusions:
- Despite severe coronary atherosclerosis, cardiac performance, including global parameters, twist, and strains, is well preserved in 6-month-old ApoE/LDLR(-/-) mice.
- Subtle diastolic alterations may indicate an ischemic background in this atherosclerosis model.
- Comprehensive MRI provides valuable insights into cardiac function in murine models of atherosclerosis.
Abstract:
ApoE/LDLR(-/-) mice represent a reliable model of atherosclerosis. However, it is not clear whether cardiac performance is impaired in this murine model of atherosclerosis. Here, we used MRI to characterize cardiac performance in vivo in apoE/LDLR(-/-) mice with advanced atherosclerosis. Six-month-old apoE/LDLR(-/-) mice and age-matched C57BL/6J mice (control) were examined using highly time-resolved cine-MRI [whole-chamber left ventricle (LV) imaging] and MR tagging (three slices: basal, mid-cavity and apical). Global and regional measures of cardiac function included LV volumes, kinetics, time-dependent parameters, strains and rotations. Histological analysis was performed using OMSB (orceine with Martius, Scarlet and Blue) and ORO (oil red-O) staining to demonstrate the presence of advanced coronary atherosclerosis. MR-tagging-based strain analysis in apoE/LDLR(-/-) mice revealed an increased frequency of radial and circumferential systolic stretch (25% and 50% of segments, respectively, p ≤ 0.012), increased radial post-systolic strain index (45% of segments, p = 0.009) and decreased LV untwisting rate (-30.3° (11.6°)/cycle, p = 0.004) when compared with control mice. Maximal strains and LV twist were unchanged. Most of the cine-MRI-based LV functional and anatomical parameters also remained unchanged in apoE/LDLR(-/-) mice, with only a lower filling rate, longer filling time, shorter isovolumetric contraction time and slower heart rate observed in comparison with control mice. The coronary arteries displayed severe atherosclerosis, as evidenced by histological analysis. Using comprehensive MRI methods, we have demonstrated that, despite severe coronary atherosclerosis in six-month-old apoE/LDLR(-/-) mice, cardiac performance including global parameters, twist and strains, was well preserved. Only subtle diastolic alterations, possibly of ischemic background, were uncovered. Copyright © 2016 John Wiley & Sons, Ltd.
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