18F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model.

Takayuki Iwaki,Hirotaka Onoe,Hiroshi Mizuma,Kazuya Hokamura,Kazuo Umemura

doi:10.1155/2016/8609274

18F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model.

Takayuki Iwaki, Hirotaka Onoe + Show 3 more

Open Access

https://doi.org/10.1155/2016/8609274

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Abstract

Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [18F]fluoro-2-deoxy-D-glucose- ([18F]FDG-) positron emission tomography (PET) has been suggested as a tool to evaluate atherosclerotic plaques by detecting accumulated macrophages associated with inflammation progress. However, at the cellular level, it remains unknown whether only macrophages exhibit high uptake of [18F]FDG. To identify the cellular origin of [18F]FDG uptake in atherosclerotic plaques, we developed a simian atherosclerosis model and performed PET and ex vivo macro- and micro-autoradiography (ARG). Increased [18F]FDG uptake in the aortic wall was observed in high-cholesterol diet-treated monkeys and WHHL rabbits. Macro-ARG of [18F]FDG in aortic sections showed that [18F]FDG was accumulated in the media and intima in the simian model as similar to that in WHHL rabbits. Combined analysis of micro-ARG with immunohistochemistry in the simian atherosclerosis model revealed that most cellular [18F]FDG uptake observed in the media was derived not only from the infiltrated macrophages in atherosclerotic plaques but also from the smooth muscle cells (SMCs) of the aortic wall in atherosclerotic lesions.

Highlights

Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses with a number of cell types and effector molecules in sequential and discrete stages [1]
Cholesterol was mostly packaged in low-density lipoprotein (LDL), which was confirmed by high performance liquid chromatography (HPLC) analysis
Though numerous studies have indicated that high [18F]FDG uptake measured by positron emission tomography (PET) is closely related to cell numbers and/or activation of infiltrated macrophages accumulated in atherosclerotic vulnerable plaques [13, 14], our study has revealed that [18F]FDG uptake was localized in both the intima and media including the smooth muscle cells (SMCs) by accurate quantification of atherosclerotic lesions at tissue and cellular levels

Summary

Introduction

Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses with a number of cell types and effector molecules in sequential and discrete stages [1]. LDLr-deficient mice (Ldlr−/−) [2] do not develop spontaneous atherosclerotic plaques with normal chow diet due to the presence of apolipoprotein-B editing catalytic polypeptide-1 (Apobec1) in their liver. Watanabe heritable hyperlipidemic (WHHL) rabbits [5], in which the LDLr is deleted [6], have been used to assess the initiation and/or progression of atherosclerotic plaques. These small animal models have been frequently used because of advantages such as easy handling, reduced ethical concerns, and wellcharacterized genetic backgrounds. Species-related differences between these animals and humans need to be considered before translating primary research data to humans

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