Author + information
- Parmanand Singh,
- Ahmed Tawakol,
- Marina Mojena,
- Maria Pimentel-Santillana,
- Zahi A. Fayad,
- James Rudd,
- Paqui G. Través,
- Maria Fernández,
- Alberto Tejedor and
- Lisardo Boscá
18F-fluorodeoxyglucose (FDG) accumulates in activated macrophages (Mø). Here, we test the hypotheses that GM-CSF, a clinically administered cytokine, augments Mø glycolysis in vitro and enhances imaging of arterial inflammation in vivo.
In vitro experiments were conducted in human and murine Mø. After GM-CSF exposure, mRNA levels were assessed for markers of M1 and M2 Mø polarization. 2D-Glc uptake was assessed before and after GM-CSF in normoxia and hypoxia. Glycolysis was evaluated at a rate-limiting step (Fru-2,6-P2 concentration) and pathway end-product conversion (lactate release). The specificity of findings with glycolysis was assessed with uPFK2 silencer RNA (siRNA). In vivo studies in NZW rabbits (n=10) were performed to determine the effect of GM-CSF on FDG uptake in normal vs inflamed arteries, using PET imaging.
Upon GM-CSF exposure, dual M1 and M2 polarization was observed, along with increased 2D-Glc uptake and glycolysis, which were both attenuated by uPFK2 siRNA (Figure 1). GM-CSF up-regulated glycolysis and 2D-Glc uptake in hypoxia and normoxia. In rabbits, there was a 73% increase in FDG uptake after GM-CSF (P<0.01), whereas there was no change after saline. In vivo FDG uptake correlated with Mø staining in pathological specimens (R=0.75, P<0.01).
GM-CSF augments glycolysis in vitro and increases FDG uptake within inflamed atheroma in vivo. Further studies should explore the role of GM-CSF to enhance the detection of inflammatory foci.
Moderated Poster Contributions
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Chronic CAD: Inflammation, Thrombosis and Calcification
Abstract Category: 33. Vascular Medicine: Basic
Presentation Number: 1153M-63
- 2013 American College of Cardiology Foundation