Effects of age, diet, and type 2 diabetes on the development and FDG uptake of atherosclerotic plaques

JACC Cardiovasc Imaging. 2011 Dec;4(12):1294-301. doi: 10.1016/j.jcmg.2011.07.009.

Abstract

Objectives: This study investigated the effects of age, duration of a high-fat diet, and type 2 diabetes on atherosclerotic plaque development and uptake of (18)F-fluorodeoxyglucose ((18)F-FDG) in 2 mouse models.

Background: The animal's age and start time and duration of a high-fat diet have effects on plaque composition in atherosclerotic mice.

Methods: The aortas of atherosclerotic low-density lipoprotein receptor deficient mice expressing only apolipoprotein B100 (LDLR(-/-)ApoB(100/100)) and atherosclerotic and diabetic mice overexpressing insulin-like growth factor II (IGF-II/LDLR(-/-)ApoB(100/100)) were investigated at 4, 6, and 12 months of age and older after varying durations of high-fat diet. C57BL/6N mice on normal chow served as controls. Plaque size (intima-to-media ratio), macrophage density (Mac-3 staining), and plaque uptake of (18)F-FDG were studied by means of in vivo positron emission tomography/computed tomography by ex vivo autoradiography and by histological and immunohistochemical methods.

Results: From the ages of 4 to 6 months and 12 months and older, the plaque size increased and the macrophage density decreased. Compared with the controls, the in vivo imaging showed increased aortic (18)F-FDG uptake at 4 and 6 months, but not at 12 months and older. Autoradiography showed focal (18)F-FDG uptake in plaques at all time points (average plaque-to-normal vessel wall ratio: 2.4 ± 0.4, p < 0.001) with the highest uptake in plaques with high macrophage density. There were no differences in the plaque size, macrophage density, or uptake of (18)F-FDG between LDLR(-/-)ApoB(100/100) and IGF-II/LDLR(-/-)ApoB(100/100) mice at any time point.

Conclusions: The 6-month-old LDLR(-/-)ApoB(100/100) and IGF-II/LDLR(-/-)ApoB(100/100) mice demonstrated highly inflamed, large, and extensive atherosclerotic plaques after 4 months of a high-fat diet, presenting a suitable model for studying the imaging of atherosclerotic plaque inflammation with (18)F-FDG. The presence of type 2 diabetes did not confound evaluation of plaque inflammation with (18)F-FDG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Animals
  • Aorta / diagnostic imaging
  • Aorta / pathology
  • Aortography
  • Apolipoprotein B-100 / genetics
  • Apolipoprotein B-100 / metabolism
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / etiology*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Autoradiography
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Immunohistochemistry
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Multimodal Imaging*
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / etiology*
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Positron-Emission Tomography*
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptor, IGF Type 2 / genetics
  • Receptor, IGF Type 2 / metabolism
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Risk Factors
  • Tomography, X-Ray Computed*

Substances

  • Apolipoprotein B-100
  • Radiopharmaceuticals
  • Receptor, IGF Type 2
  • Receptors, LDL
  • Fluorodeoxyglucose F18