Apolipoprotein E Deficiency Produces an Inflammatory Abdominal Aortic Aneurysm in a Rat Calcium Chloride-Induced Model.

INTRODUCTION: The goal of this work is to characterize a novel model of abdominal aortic aneurysm (AAA) in Apolipoprotein E-knockout (ApoE(-/-)) rats. We hypothesize that ApoE(-/-) rats will exhibit an increased inflammatory response and exacerbated AAA compared to wild-type (WT) rats. MATERIALS AND METHODS: AAA was induced in male and female Lean Zucker ApoE(-/-) and WT rats via periadventitial calcium chloride exposure. Aortic dilation was measured via ultrasound and photomicrograph. Rats were euthanized 35 d after AAA induction. Aortic tissues were analyzed for morphology, lipid deposition, macrophage infiltration, and matrix metalloproteinase (MMP) levels. RESULTS: Total cholesterol, low-density lipoprotein, and triglyceride levels were significantly elevated in ApoE(-/-) rats. ApoE(-/-) rats had >6-fold aortic wall lipid deposition (19.1 ± 5.8 × 10(-3)versus 2.9 ± 2.9 × 10(-3) mm(2), P < 0.0001) and >4-fold macrophage infiltration within the intimal and medial layers (14.0 ± 7.1 × 10(-4)versus 3.5 ± 2.1 × 10(-4) mm(2), P = 0.0001) versus WT rats. At euthanasia, ApoE(-/-) rats showed significantly greater increased aortic diameter (58.1 ± 10.7%) than WT rats (42.5 ± 15.4%, P = 0.00081). Interestingly, male ApoE(-/-) rats had significantly greater increased aortic diameter (63.6 ± 10.2%) than male WT rats (45.4 ± 16.7%, P = 0.0262), but no significant difference was observed between female ApoE(-/-) and WT rats. Lastly, aortic levels of MMP-2 and MMP-12 were significantly higher in ApoE(-/-)versus WT rats, with considerable sex differences observed. CONCLUSIONS: Our work demonstrates that the absence of ApoE results in more aggressive aneurysm formation with increased inflammation and notable differences between sexes. These data expand on current rat AAA models and create a rodent model that more closely resembles human AAA.