18F-fluorodeoxyglucose PET-MR characterization of aortic inflammation in ApoE-/- mouse models of accelerated atherosclerosis: comparison of Western diet vs. uremia

Int J Cardiovasc Imaging. 2024 Nov;40(11):2335-2344. doi: 10.1007/s10554-024-03238-0. Epub 2024 Sep 21.

Abstract

ApoE-/- mice are a widely used preclinical model of atherosclerosis, potentially accelerated by a Western diet (WD) or uremia. We aimed to compare hybrid 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-magnetic resonance (PET-MR) and immunostaining in ApoE-/- models of accelerated atherosclerosis. Five groups were studied: standard diet-fed ApoE-/- (n = 7), standard diet-fed and uremic ApoE-/- (n = 7), WD ApoE-/- (n = 7), WD and uremic ApoE-/- (n = 6), and control C57BL/6J mice (n = 6). Uremia was induced by electrocoagulation of the right kidney at 8 weeks old, followed 2 weeks later by a contralateral nephrectomy. 18F-FDG PET-MR imaging and histological staining (anti-CD4, -CD8, -CD11c, -CD20, -CD31, -CD68, -CD163, -interferon-γ, interleukin-1α, -1β, -6, -17 A antibodies) were performed in 18-week-old mice, i.e., 8 weeks after 5/6 nephrectomy and/or WD. 18F-FDG uptake was similar in all groups. In contrast, histological staining highlighted higher percentages of CD8-, CD68-, or CD11c-positive cells in ApoE-/- aortic samples than in wild-type aortic samples. In addition, immunostaining revealed some differences between ApoE-/- mouse groups. Only the WD seemed to contribute to these differences. Using immunostaining, WD appeared to be a stronger accelerator of atherosclerosis than uremia. However, 18F-FDG PET-MR imaging failed to demonstrate in vivo increased aortic glucose uptake in these models.

Keywords: ApoE −/−; Atherosclerosis; PET-MR; Uremia; Western diet.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aorta / diagnostic imaging
  • Aorta / metabolism
  • Aorta / pathology
  • Aortitis* / diagnostic imaging
  • Aortitis* / etiology
  • Aortitis* / metabolism
  • Aortitis* / pathology
  • Apolipoproteins E
  • Atherosclerosis* / diagnostic imaging
  • Atherosclerosis* / etiology
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • Diet, Western* / adverse effects
  • Disease Models, Animal*
  • Fluorodeoxyglucose F18* / administration & dosage
  • Magnetic Resonance Imaging
  • Male
  • Mice, Inbred C57BL*
  • Mice, Knockout, ApoE*
  • Multimodal Imaging
  • Plaque, Atherosclerotic*
  • Positron-Emission Tomography*
  • Predictive Value of Tests*
  • Radiopharmaceuticals*
  • Time Factors
  • Uremia* / diagnostic imaging
  • Uremia* / metabolism

Substances

  • Fluorodeoxyglucose F18
  • Radiopharmaceuticals
  • Apoe protein, mouse
  • Apolipoproteins E