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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2016

Open Access 01-12-2016 | Original investigation

Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer 18F-fluoromethylcholine

Authors: Sanna Hellberg, Johanna M. U. Silvola, Max Kiugel, Heidi Liljenbäck, Olli Metsälä, Tapio Viljanen, Jari Metso, Matti Jauhiainen, Pekka Saukko, Pirjo Nuutila, Seppo Ylä-Herttuala, Juhani Knuuti, Anne Roivainen, Antti Saraste

Published in: Cardiovascular Diabetology | Issue 1/2016

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Abstract

Background

Diabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice.

Methods

Low-density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin-like growth factor II (IGF-II/LDLR−/−ApoB100/100 and LDLR−/−ApoB100/100) were studied. Distribution kinetics of choline analogue 18F-fluoromethylcholine (18F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of 18F-FMCH and glucose analogue 18F-fluorodeoxyglucose (18F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The 18F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers.

Results

The aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of 18F-FMCH was rapid. Both the absolute 18F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non-diabetic mice. In autoradiography, the highest 18F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. 18F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with 18F-FDG, 18F-FMCH provided similar or higher plaque-to-background ratios in diabetic mice.

Conclusions

Type 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer 18F-FMCH is a potential tool to study vascular inflammation associated with diabetes.
Appendix
Available only for authorised users
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Metadata
Title
Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer 18F-fluoromethylcholine
Authors
Sanna Hellberg
Johanna M. U. Silvola
Max Kiugel
Heidi Liljenbäck
Olli Metsälä
Tapio Viljanen
Jari Metso
Matti Jauhiainen
Pekka Saukko
Pirjo Nuutila
Seppo Ylä-Herttuala
Juhani Knuuti
Anne Roivainen
Antti Saraste
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2016
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-016-0340-6

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