Abstract
An abdominal aortic aneurysm (AAA) is an enlargement of the greatest artery in the body defined as an increase in diameter of 1.5-fold. AAAs are common in the elderly population and thousands die each year from their complications. The most commonly used mouse model to study the pathogenesis of AAA is the angiotensin II (Ang II) infusion method delivered via osmotic mini-pump for 28 days. Here, we studied the site-specificity and onset of aortic rupture, characterized three-dimensional (3D) images and flow patterns in developing AAAs by ultrasound imaging, and examined macrophage infiltration in the Ang II model using 65 apolipoprotein E-deficient mice. Aortic rupture occurred in 16 mice (25%) and was nearly as prevalent at the aortic arch (44%) as it was in the suprarenal region (56%) and was most common within the first 7 days after Ang II infusion (12 of 16; 75%). Longitudinal ultrasound screening was found to correlate nicely with histological analysis and AAA volume renderings showed a significant relationship with AAA severity index. Aortic dissection preceded altered flow patterns and macrophage infiltration was a prominent characteristic of developing AAAs. Targeting the inflammatory component of AAA disease with novel therapeutics will hopefully lead to new strategies to attenuate aneurysm growth and aortic rupture.
Highlights
The abdominal aortic aneurysm (AAA) is a localized dilatation of the abdominal aorta exceeding the normal diameter by more than 50% (Upchurch and Schaub, 2006)
angiotensin II (Ang II)-induced aortic rupture occurs in the abdominal aorta and in the thoracic region In this study, 65 apoE−/− male mice were implanted with Ang II pumps at a delivery rate of 1 μg/kg/min for 4 weeks
Twenty-four mice (37%) did not develop a detectable AAA according to standard criteria (i.e., 1.5-fold increase in suprarenal diameter), despite full release of Ang II from the pumps, while 41 mice (63%) developed aortic aneurysms, with 25 surviving to the study endpoint (Table 1)
Summary
The abdominal aortic aneurysm (AAA) is a localized dilatation of the abdominal aorta exceeding the normal diameter by more than 50% (Upchurch and Schaub, 2006). AAAs are associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and a genetic predisposition (van Vlijmen-van Keulen et al, 2002; Golledge et al, 2006; Lloyd-Jones et al, 2010). AAAs are becoming common vascular disorders with life-threatening implications such as aortic rupture, which has been reported to have a mortality rate as high as 90% (Lloyd-Jones et al, 2010). Understanding the pathophysiology of AAAs and translating the knowledge from basic science to the clinical realm is certain to be a promising step to prevent this condition
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