In vivo detection of urokinase-type plasminogen activator receptor (uPAR) expression in arterial atherogenesis using [
Arteries
/ metabolism
Atherosclerosis
/ diagnostic imaging
Copper Radioisotopes
Heterocyclic Compounds, 1-Ring
Humans
Oligopeptides
Plaque, Atherosclerotic
Positron Emission Tomography Computed Tomography
Positron-Emission Tomography
/ methods
Receptors, Urokinase Plasminogen Activator
/ genetics
Retrospective Studies
Urokinase-Type Plasminogen Activator
Atherosclerosis
Atherosclerotic plaque
Molecular imaging
Mononuclear phagocyte system (MPS)
Positron-emission tomography (PET)
Urokinase-type plasminogen activator receptor (uPAR)
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
19
10
2021
revised:
23
02
2022
accepted:
25
03
2022
pubmed:
10
4
2022
medline:
29
6
2022
entrez:
9
4
2022
Statut:
ppublish
Résumé
Urokinase-type plasminogen activator receptor (uPAR) is associated with extracellular matrix (ECM) degradation and cancer aggressiveness. Its role in arterial atherogenesis as a molecular imaging target is not well-established. The aim of this study was to non-invasively visualize uPAR expression in atherosclerosis by a novel uPAR-targeting positron emission tomography (PET) tracer [ We used molecular biology to investigate uPAR expression by analyzing human atherosclerotic plaques and cultured cells. A retrospective analysis was performed on patients, who underwent combined PET/CT (n = 10) to measure [ The in vitro assay for THP-1 monocytes displayed a significantly upregulated uPAR expression upon stimulation (5.2-fold upregulation, p < 0.0001 by a one-way ANOVA followed by Tukey's test) by single-cell flowcytometric analysis. Freshly excised human atherosclerotic plaques underwent flow cytometric and microarray analyses manifesting 73.9 ± 2.9% of mononuclear phagocyte system (MPS) cells expressing uPAR and had a greater than 7-fold higher gene expression of plasminogen activator urokinase receptor (PLAUR, p = 0.002), integrin subunit alpha X (ITGAX, p = 0.0008), and cluster of differentiation 163 (CD163, p < 0.0001). The tissue-to-background ratios (TBR uPAR is abundantly expressed by MPS cells in atherosclerotic plaques and can be visualized by the novel PET tracer [
Sections du résumé
BACKGROUND AND AIMS
Urokinase-type plasminogen activator receptor (uPAR) is associated with extracellular matrix (ECM) degradation and cancer aggressiveness. Its role in arterial atherogenesis as a molecular imaging target is not well-established. The aim of this study was to non-invasively visualize uPAR expression in atherosclerosis by a novel uPAR-targeting positron emission tomography (PET) tracer [
METHODS
We used molecular biology to investigate uPAR expression by analyzing human atherosclerotic plaques and cultured cells. A retrospective analysis was performed on patients, who underwent combined PET/CT (n = 10) to measure [
RESULTS
The in vitro assay for THP-1 monocytes displayed a significantly upregulated uPAR expression upon stimulation (5.2-fold upregulation, p < 0.0001 by a one-way ANOVA followed by Tukey's test) by single-cell flowcytometric analysis. Freshly excised human atherosclerotic plaques underwent flow cytometric and microarray analyses manifesting 73.9 ± 2.9% of mononuclear phagocyte system (MPS) cells expressing uPAR and had a greater than 7-fold higher gene expression of plasminogen activator urokinase receptor (PLAUR, p = 0.002), integrin subunit alpha X (ITGAX, p = 0.0008), and cluster of differentiation 163 (CD163, p < 0.0001). The tissue-to-background ratios (TBR
CONCLUSIONS
uPAR is abundantly expressed by MPS cells in atherosclerotic plaques and can be visualized by the novel PET tracer [
Identifiants
pubmed: 35396143
pii: S0021-9150(22)00159-9
doi: 10.1016/j.atherosclerosis.2022.03.026
pii:
doi:
Substances chimiques
Copper Radioisotopes
0
Heterocyclic Compounds, 1-Ring
0
Oligopeptides
0
Receptors, Urokinase Plasminogen Activator
0
beta-cyclohexylalanyl-phenylalanyl-seryl-arginyl-tyrosyl-leucyl-tryptophyl-serine
0
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
1HTE449DGZ
Urokinase-Type Plasminogen Activator
EC 3.4.21.73
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103-111Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.