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Microvessel Density But Not Neoangiogenesis Is Associated with 18F-FDG Uptake in Human Atherosclerotic Carotid Plaques

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Abstract

Introduction

The vulnerable atherosclerotic lesion exhibits the proliferation of neovessels and inflammation. The imaging modality 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (18FDG-PET) is considered for the identification of vulnerable plaques.

Purpose

The purpose of this study was to compare the gene expression of neoangiogenesis and vulnerability-associated genes with 18FDG uptake in patients undergoing carotid endarterectomy.

Procedures

Human atherosclerotic carotid artery plaques from symptomatic patients were used for gene expression analysis by quantitative PCR of vascular endothelial growth factor (VEGF) and integrin αV and integrin β3 subunits, genes essential during neoangiogenesis. We also evaluated the gene expression of CD34, a measure of microvessel density (MVD), as well as CD68, MMP-9, and cathepsin K, genes of major importance in plaque vulnerability. Gene expression analysis was compared with 18FDG-PET.

Results

VEGF and integrin αVβ3 gene expression did not correlate with 18FDG uptake, whereas CD34 gene expression exhibited an inverse correlation with 18FDG uptake. Additionally, we established that markers of vulnerability were correlated with 18FDG uptake.

Conclusions

Neoangiogenesis is not associated with 18FDG uptake, whereas MVD and markers of vulnerability correlate with 18FDG uptake. The absence of correlation between markers of neoangiogenesis and 18FDG uptake suggests a temporal separation between the process of neoangiogenesis and inflammatory activity.

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Acknowledgments

The financial support from The Danish Heart Foundation, The Research Fund of Rigshospitalet, The Danish Medical Research Council, The John and Birthe Meyer Foundation, General-consul Friedrich Bøhm and daughter Else Bøhms Foundation, Tove and Richard Severin Hansens Grant, The Oticon Foundation, and finally The Refuge of Løgumkloster is gratefully acknowledged. The PET/CT scanner was donated by the John and Birthe Meyer Foundation. The authors wish to thank Jytte Oxbøl for providing qPCR designs for the measurement of markers of neoangiogenesis as well as all medical laboratory technologists involved in helping out with the PET/CT scans.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cluster for Molecular Imaging, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark

    Sune Folke Pedersen, Anne Mette Fisker Hag, Liselotte Hoejgaard & Andreas Kjaer

  2. Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2200, Copenhagen, Denmark

    Sune Folke Pedersen, Anne Mette Fisker Hag, Liselotte Hoejgaard & Andreas Kjaer

  3. Department of Vascular Surgery, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2200, Copenhagen, Denmark

    Martin Graebe & Henrik Sillesen

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  1. Sune Folke Pedersen
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  2. Martin Graebe
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Correspondence to Sune Folke Pedersen.

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Pedersen, S.F., Graebe, M., Hag, A.M.F. et al. Microvessel Density But Not Neoangiogenesis Is Associated with 18F-FDG Uptake in Human Atherosclerotic Carotid Plaques. Mol Imaging Biol 14, 384–392 (2012). https://doi.org/10.1007/s11307-011-0507-1

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