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- Title
<sup>18</sup>F-FDG PET Imaging of Murine Atherosclerosis: Association with Gene Expression of Key Molecular Markers.
- Authors
Hag, Anne Mette Fisker; Pedersen, Sune Folke; Christoffersen, Christina; Binderup, Tina; Jensen, Mette Munk; Jørgensen, Jesper Tranekjær; Skovgaard, Dorthe; Ripa, Rasmus Sejersten; Kjaer, Andreas
- Abstract
Aim:To study whether 18F-FDG can be used for in vivo imaging of atherogenesis by examining the correlation between 18FFDG uptake and gene expression of key molecular markers of atherosclerosis in apoE-/- mice. Methods:Nine groups of apoE-/- mice were given normal chow or high-fat diet. At different time-points, 18F-FDG PET/ contrast-enhanced CT scans were performed on dedicated animal scanners. After scans, animals were euthanized, aortas removed, gamma counted, RNA extracted from the tissue, and gene expression of chemo (C-X-C motif) ligand 1 (CXCL-1), monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, cluster of differentiation molecule (CD)-68, osteopontin (OPN), lectin-like oxidized LDL-receptor (LOX)-1, hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGF), and tissue factor (TF) was measured by means of qPCR. Results:The uptake of 18F-FDG increased over time in the groups of mice receiving high-fat diet measured by PET and ex vivo gamma counting. The gene expression of all examined markers of atherosclerosis correlated significantly with 18F-FDG uptake. The strongest correlation was seen with TF and CD68 (p<0.001). A multivariate analysis showed CD68, OPN, TF, and VCAM-1 to be the most important contributors to the uptake of 18F-FDG. Together they could explain 60% of the 18F-FDG uptake. Conclusion:We have demonstrated that 18F-FDG can be used to follow the progression of atherosclerosis in apoE-/- mice. The gene expression of ten molecular markers representing different molecular processes important for atherosclerosis was shown to correlate with the uptake of 18F-FDG. Especially, the gene expressions of CD68, OPN, TF, and VCAM-1 were strong predictors for the uptake.
- Subjects
GENE expression; BIOMARKERS; ATHEROSCLEROSIS; HYPOXEMIA; MOLECULES; CELL adhesion molecules
- Publication
PLoS ONE, 2012, Vol 7, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0050908