Abstract
Objectives
We present a method to quantify the inflammatory processes that drive abdominal aortic
aneurysm (AAA) development that may help predict the rate of growth and thus guide
medical and surgical management. We use an in vivo optical molecular imaging approach
to quantify protease activity within the walls of AAAs in a rodent model.
Methods
AAAs were generated in mice by topical application of calcium chloride, followed by
the administration of the MMP inhibitor doxycycline for 3 months. After this time
period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity
was administered, and MMP proteolytic activity was measured in vivo. Histology and
in situ zymography were performed for validation. AAAs were also generated in rats,
and MMP activity within the walls of the AAAs was also quantified endovascularly.
Results
A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated,
with high doses of the drug resulting in nearly complete suppression of aneurysm formation.
There was a direct relationship between the rate of aneurysmal growth and measured
MMP activity, with a linear best-fit well approximating the relationship. We additionally
performed endovascular imaging of AAAs in rats and demonstrated a similar suppression
of intramural MMP activity following doxycycline administration.
Conclusions
We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents
and show a direct, linear relationship between proteolytic activity and aneurysmal
growth. We also illustrate that this functional imaging method can be performed endovascularly,
demonstrating potential pre-clinical and clinical applications.
Keywords
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Article Info
Publication History
Published online: June 14, 2010
Accepted:
May 8,
2010
Received in revised form:
February 23,
2010
Received:
November 14,
2009
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
