Abstract 16206: Quantitative Detection of Diet-Induced Plaque Endothelial Erosion and Recovery in ApoE-/- Mice Using Semipermeant Nanoparticles and Fluorine Magnetic Resonance Spectroscopy
Introduction: Acute atherothrombotic occlusion in heart attack and stroke implies disruption of the vascular endothelial barrier that exposes a highly procoagulant intimal milieu. However, the severity of vascular barrier damage in advanced atherosclerotic plaques and its recovery in response to therapeutic intervention remain unknown due in part to the lack of quantitative methods for in vivo assessment. Here, we report that semipermeant perfluorocarbon nanoparticles (PFC NPs) used in conjunction with 19F magnetic resonance spectroscopy (19F MRS) permit quantification of diet-induced endothelial barrier disruption and recovery in ApoE-/- mice.
Methods and Results: Forty ApoE-/ mice were placed on either a normal chow (n = 16) or high-fat (n = 24) diet. After 4 months on high-fat diet, 8 mice (4 mice per group) were switched to normal chow for either 1 month or 2 months. At selected time points, mice were injected with Rhodamine B labeled PFC NPs, which were allowed to circulate in vivo for 2 hours. Subsequently, aortas were removed for fluorescence imaging or 19F MRS to quantify total PFC NP accumulation. By 4 months, the high-fat diet had induced sufficient endothelial disruption to permit intimal PFC NP accumulation (Fig. A and B, 0.13 ± 0.04 μL/g, n = 3). After 1 month off diet, cholesterol levels returned to baseline (413.9 ± 49.8 mg/dL) but aortic PFC NP levels remained stable (0.14 ± 0.02 μL/g, n = 4). After 2 months off diet, aortic PFC NP levels (0.07 ± 0.01 μL/g, n = 4) decreased to become equivalent to those of normal chow mice (p = 0.28) while levels in fat-fed mice continued to rise (p = 0.002).
Conclusions: Diet-induced erosion of plaque endothelium permits intimal PFC NP accumulation and can be reversed with dietary restriction. PFC NPs and 19F MRS/MRI could serve as useful tools to noninvasively quantify endothelial barrier disruption.
- © 2013 by American Heart Association, Inc.