Published Online
on September 17, 2008

A more recent version of this article appeared on November 1, 2008

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Original Article

In Vivo Serial Assessment of Aortic Aneurysm Formation in apoE-/- Mice via Magnetic Resonance Imaging

Gregory H Turner; Alan R Olzinski; Roberta E Bernard; Karpagam Aravindhan; Heather W Karr; Rosanna C Mirabile; Robert N Willette; Peter J Gough and Beat M Jucker¹

GlaxoSmithKline, King of Prussia, PA

¹ E-mail: beat.m.jucker{at}gsk.com

Background—Hyperlipidimic mice administered angiotensin-II (Ang-II) have been used for the study of abdominal aortic aneurysms (AAA). The purpose of this study was to examine the utility of magnetic resonance imaging (MRI) for studying AAA development and for examining the effects of pharmacological intervention on AAA development in the apoE-/- mouse.

Methods and Results—Suprarenal aortic aneurysms were generated in apoE-/- mice administered Ang-II (1000 ng/kg/min) for up to 28 days. In vivo MRI was performed serially (once weekly) to assess AAA development and rupture. Comparison of AAA size as measured by in vivo and ex vivo MRI resulted in excellent agreement (r=0.96, P<0.0001). Additionally, MRI correlated with histology derived AAA area assessment (r=0.84, in vivo vs. histology; P<0.0001 and r=0.89, ex vivo vs. histology; P<0.0001). In a separate study, Ang-II administered apoE-/- mice were treated with doxycycline (broad based matrix metalloproteinase inhibitor, 30 mg/kg/day for 28 days). MRI was able to non-invasively assess a reduced rate of AAA development (46% vs. 71%, P<0.05), a decreased AAA area (2.56 mm2 vs. 4.02 mm2, P<0.01), and decreased incidence of rupture (43% vs. 100%) in treated vs. control animals. Inhibition of aorta MMP2/9 activity was observed in the treated animals.

Conclusions—These results demonstrate the utility of MRI to assess non-invasively and temporally AAA development upon pharmacological intervention in this pre-clinical cardiovascular disease model.

Key Words: abdominal aortic aneurysms • imaging • MRI • doxycycline • MMP