Supplementary Material for: Angiotensin II Infusion Does Not Cause Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Rats

The apolipoprotein E-deficient (apoE-/-)
mouse model has advanced our understanding of cardiovascular disease
mechanisms and experimental therapeutics. This spontaneous model
recapitulates aspects of human atherosclerosis, and allows for the
development of dissecting abdominal aortic aneurysms (AAAs) when
combined with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar to mice, they would develop dissecting AAAs. We created rats with a 16-bp deletion of the apoE
gene using transcription activator-like effector nucleases. We imaged
the suprarenal aorta for 28 days after implantation of miniosmotic pumps
that infuse angiotensin II (AngII, 200 ng/kg/min). Blood pressure (BP),
serum lipids and lipoproteins, and histology were also analyzed. These
rats did not develop pathological aortic dissection, but we did observe a
decrease in circumferential cyclic strain, a rise in BP, and
microstructural changes in the aortic medial layer. We also measured
increased serum lipids with and without administration of a high-fat
diet, but did not detect atherosclerotic plaques. Chronic infusion of
AngII did not lead to the formation of dissecting AAAs or
atherosclerosis in the rats used in this study. While reduced amounts of
atherosclerosis may explain this resistance to dissecting aneurysms,
further investigation is needed to fully characterize species-specific
differences.