Table III.
Summary of how animal models reflect risk factors and observations from human disease
| Risk factor | Significance in human AAA | Model | Reflection in murine models |
|---|---|---|---|
| Age | Age-dependent increasing incidence of AAA4 | PPE AngII |
Mainly 10 week-old-mice treated11,23,32,85; bigger AAA in PPE in older mice (unpublished); higher incidence of AngII dissection in older animals30 |
| Family history | Higher prevalence if one sibling is affected, higher in twins86 | – | Not applicable |
| Ethnicity | Highest prevalence in Caucasians87 | ePPE AngII |
Different susceptibilities to the induction stimuli in mice from different strains (ie, size, VSMC biology)88,89 |
| Smoking | Major risk factor for AAA and associated with faster aneurysm growth4,87 | AngIIPPE | Nicotine instigates AAA formation, increases the incidence (AngII) and promotes AAA growth, rupture. and arterial stiffness45,57,85,90, 91, 92, 93, 94, 95 |
| Male sex | Higher AAA incidence in men, worse outcomes after aortic repair in women26,96 | AngII PPE |
Aneurysm formation 5-10 times higher in male mice97 Female sex hormones prevent AAA formation98 |
| Hypertensive disease | Major risk factor for AAA | AngII | Aneurysm formation/dissection is not associated with hypertension99 |
| Metabolic syndrome | No direct association | AngII | AAA incidence 3-4 times higher in hypercholesterolemic mice53,100 |
| Connective tissue disease | Variety of aortic and other aneurysms in patients with a variety of CTD101 | – | Individual mouse models with specific mutations, but no combination with AAA models102 |
| Observation | |||
| Disturbed/altered iliac outflow | Progressive AAA kinking and higher AAA incidence103 | PPE | Promotes AAA kinking and catalyzes potential adventitial angiogenesis32,104 |
| Metformin | possibly protective of AAA105 | AngII | slows AAA/dissection growth106,107 |
| Statins | Statins reduce AAA growth and AAA-related mortality4,26 | AngII PPE |
Statins suppress AAA formation in normal and hypercholesterolemic mice108,109 |
| Platelet inhibitors | Recommended in patients with AAA to lower cardiovascular comorbidities4 | AngII | Decreased the increase of aortic diameter, leukocyte infiltration, MMP9 expression and elastic fiber degradation110,111 |
| ILT | Viscoelastic, biologically active thrombus observed in >90% of AAAs26 | ePPE | Observed regularly, currently no data on biological activity12 |
| Atherosclerotic aorta | High coincidence of atherosclerosis and AAA in human, yet considered distinct diseases52 | AngII CaCl2 PPE ePPE |
See section above on the significance of the atherosclerotic murine aorta |
| AAA localization | >80% infrarenal26 | AngII CaCl2 PPE ePPE |
AngII aortic dissections are seen mostly at the ascending and thoracoabdominal portion of the aorta proximal to the renal arteries29 for the other models, the localization is subject to surgical exposure (Fig 4) |
| Rupture | Most frequently contained into retroperitoneal space4 | AngII ePPE | AngII: open rupture or intramural bleeding29 ePPE: open rupture or contained to retroperitoneal space12 |
AAA, Abdominal aortic aneurysm; AngII, angiotensin II; CTD, connective tissue disease; ePPE, external periadventitial elastase application; ILT, intraluminal thrombus; MMP, matrix metalloproteinase; PPE, periadventitial elastase application; VSMC, vascular smooth muscle cell.