Abstract 1644: p38 MAPK Inhibition Reduces Aortic Ultrasmall Superparamagnetic Iron Oxide Contrast Agent Uptake as Assessed by MRI in an Atherosclerotic Mouse Model
Background: Ultrasmall superparamagnetic iron oxide (USPIO) has been used as a contrast agent for non-invasive MRI assessment of atherosclerotic plaque inflammation. However, USPIO assessment in mouse atherosclerosis models has been limited. The purpose of this study was to non-invasively evaluate USPIO uptake in the aortic arch of Angiotensin II (Ang II) administered apoE−/− mice in the presence of anti-inflammatory, p38 MAPK inhibition.
Methods and Results: 28 wk old apoE−/− mice were infused for 21 days with saline or Ang II (1.44 mg/kg/day). Dietary administration of the p38 MAPK inhibitor (SB-239063, 150 mg/kg/day) was initiated one week prior to Ang II administration (Ang II+SB-239063). On both day 19 and 20 all mice received an iv injection of USPIO (Combidex®, 1000 umol/kg) followed by in vivo MRI of the aortic arch. Absolute Iron analyses of the aortic arch and ex vivo MRI of the aortic root were performed. Plasma MCP-1 and MIP-1b were significantly elevated in the Ang II, but not in the Ang II+SB-239063 group. In vivo USPIO uptake in the aortic arch was observed by MRI in all animals. However, while the Ang II group had significantly higher absolute iron content (↑103%, P<0.001) in the aorta compared with the saline group, the Ang II+SB-239063 group did not (↑6%, NS). Both MRI signal intensity of the aortic arch and aortic root were significantly correlated to the absolute iron content in the aortic arch.
Conclusion: The present study demonstrates that non-invasive assessment of USPIO uptake, as a marker for inflammation in mouse atherosclerotic plaque, is feasible and that p38 MAPK inhibition attenuates the pro-inflammatory uptake of USPIO in the aorta of Ang II infused apoE−/− mice.