Abstract 1166: In-vivo Serial Assessment of Aortic Aneurysm Formation in a Hyperlipidimic Mouse Model
Introduction Abdominal aortic aneurysms (AAA) can be consistently produced in hyperlipidimic mice by continuous infusion of Angiotensin-II (Ang-II). MRI allows for AAA visualization in-vivo with sufficient spatial resolution to assess changes in aneurysm size and morphology. Bright-blood contrast allows for detection of medial breaks, an index of AAA severity, and USPIO contrast agent uptake allows for detection of macrophage activity in AAA. For this study we used MRI to characterize AAA development in a murine model and examined the effect of the broad-based MMP inhibitor, doxycycline, on AAA progression over a 4 week period.
Methods Osmotic pumps were implanted subcutaneously in ApoE−/− mice for infusion of Ang-II (1000 ng/kg/min) over 4 weeks. Animals were given 30 mg/kg/day doxycycline or vehicle (n=15 per group) via drinking water. Weekly scans were performed using a 9.4T MRI scanner. In addition, uptake of USPIO (Combidex, 1000 μmol/kg) in AAA was measured.
Results MRI revealed two distinct features of AAA development: remodeling of the adventitia which compresses the aortic lumen (Fig 1B⇓) and a break in the medial wall characterized by bright-blood signal within the AAA (Fig 1C⇓). Higher incidence of AAA formation in the vehicle vs. doxycycline group was detected along with a significantly larger (P<.01) AAA area. For mice given USPIO, MRI revealed signal loss in the periphery and shoulder region of the AAA which corresponded to macrophage rich regions as determined by IHC.
Conclusion These results demonstrate MRI’s potential for non-invasively and temporally assessing AAA development and pharmacological intervention in this pre-clinical cardiovascular disease model.