Early development in a murine model of abdominal aortic aneurysms

In vivo imaging of vascular disease models has been largely underutilized, but it can greatly benefit cardiovascular research. An improved understanding of the development of the angiotensin II (AngII) apolipoprotein E... [ view full abstract ]

In vivo imaging of vascular disease models has been largely underutilized, but it can greatly benefit cardiovascular research. An improved understanding of the development of the angiotensin II (AngII) apolipoprotein E knockout (apoE-/-) model of abdominal aortic aneurysms (AAAs) could help patients with this life-threatening disease.
The objective of this study is to investigate the early hemodynamic, biomechanical, and volumetric changes in AngII AAAs using high-frequency ultrasound. In parallel, we aim to investigate early pro-inflammatory gene expression of AAAs.
Five male apoE-/- mice were subcutaneously implanted with AngII-loaded miniosmotic pumps (1000 ng/kg/min) and screened for appearance of AAAs in our initial study.
We found that biomechanical and hemodynamic changes occurred during initial AAA formation alongside an increase in AAA volume. Average AAA volume increased by 140±24% between baseline and AAA diagnosis, while true lumen volume decreased by 46±12% due to formation of a focal dissection. The resulting intramural thrombus evolved in shape and volume but with variability between animals. We observed regional differences in blood flow through AAAs and mean blood flow velocity significantly increased by 150±42% upon initial aortic expansion due to true lumen narrowing. Circumferential cyclic strain also significantly decreased and remained reduced, indicating the AAAs had stiffened vessel walls.
Gene expression analysis of aortic tissue from apoE-/- mice has shown that two pro-inflammatory protein factors (MCP-1 and IL-1β) have higher levels of transcription relative to wildtype mice.
Our ongoing work aims to screen mice for AAAs, acquire high-resolution ultrasound data, and analyze RNA expression after AAA formation.