A Structurally Based Investigation of Abdominal Aortic Aneurysms in Mouse Models

Understanding the mechanical properties of Abdominal Aortic Aneurysms is paramount to improving treatment of this deadly condition. Here, we present work that makes strides in understanding not only the mechanical behavior and constitutive parameters of the two vessels that experience AAAs in different models, but also the effects of three major components of AAA formation. Biaxial mechanical tests were performed using a modified computer- controlled device. We examined the solid mechanics of the infrarenal and suprarenal aorta to examine why non-targeted models of AAAs (like Ang-II infusion) form exclusively in the suprarenal aorta whereas in humans the lesions preferentially form in the infrarenal aorta. The major difference between the two vessels is the elastin content and lamellar thickness in the suprarenal aorta. We analyzed the mechanical and constitutive effects of an acute loss of functional elastin via intraluminal exposure to elastase. We found that after elastase exposure, vessels were less distensible and experienced non-uniform, but modest dilatation. The constitutive parameters reflect elastin loss and increased collagen loading. We detailed the loss of smooth muscle cell contractility as found in human lesions that form in the thoracic aorta. We examined wild-type (WT), heterozygous (HET), and null (KO) a-smooth muscle actin (a-SMA) mice. The data and associated constitutive parameters were nearly identical amongst the three groups. We studied the biaxial mechanical tests on Angiotensin-II-infused ApoE-/- mice. This model is common model of AAA; however, instead of dilation and a thinning of the wall as in AAAs, Ang-II results in a dissecting aneurysm with adventitial growth. The pressure-diameter curves show a lack of sigmoidal shape attributed to elastin, there is some distensibility. The pressure-force behavior of these vessels is similar to a native vessel, unlike the pressure-force behavior of the elastase vessels. We have added a piece to the puzzle in understanding why AAAs occur preferentially in the suprarenal in mice as opposed to the infrarenal in humans. Our work with the a-SMA mice, introduces the idea that missense mutations in the ACTA2 gene, rather than the knocking out of the gene, leads to vascular diseases. We have increased the knowledge of the Ang-II infusion model by presenting biaxial mechanical data of the resulting dilatations. We have also further explored this widely used AAA model via histology to determine that in it is not a model for aneurysm development, but is a dissecting adventitial disease.