Mechanobiology of aortic disease in animal models
Abstract/Contents
- Abstract
- The aorta is the largest blood vessel in the body, responsible for carrying blood from the heart directly to most major organs and ending at the iliac arteries which feed the lower extremities. This elastic vessel provides much of the vascular system's compliance and is composed of a heterogeneous mixture of smooth muscle cells, collagen, and elastin. The general purpose of our work has been to use in vivo imaging to determine abdominal aortic dynamics in a variety of healthy and diseased cases. First, a cross-species analysis in mice, rats, rabbits, pigs and humans showed with M-mode ultrasound that infrarenal abdominal aortic motion was similar in animals and humans, regardless of aortic size. Greater anterior than posterior wall motion was observed and aortic wall displacement increased linearly with diameter. Next, cardiovascular abnormalities in a recently developed mouse model for Williams-Beuren Syndrome (WBS) were investigated. WBS is a rare genetic disorder caused by a heterozygous 1.5-megabase deletion, which typically includes the elastin gene. In this study, we showed that Wbs mice have hypertension, reduced in vivo cyclic strain, and fragmented medial elastin sheets - all characteristics similar to human WBS. These data provide insight into the genotype-phenotype relationship between elastin levels, aortic stiffness, and the cardiovascular abnormalities associated with WBS and other microdeletion syndromes. Finally, the biomechanical influences on murine models of abdominal aortic aneurysms (AAA), a pathological dilation of the abdominal aorta, were investigated using magnetic resonance imaging. From this work, we showed that the location of aneurysm development may be correlated with the location of maximum abdominal aortic curvature in angiotensin II-induced murine AAAs. This model consistently forms abdominal aneurysms with repeatable leftward vessel expansion above the renal arteries. Our work has shown that this leftward saccular shape is likely influenced by leftward suprarenal aortic curvature and motion. Histological analysis provided evidence for degradation of medial elastin at one focal location on the left side of the vessel, with a majority of animals also developing an adventitial hematoma at a similar circumferential location. Conversely, elastase-induced infrarenal murine AAAs do not form in a location of high vessel curvature and do not expand in one general direction. This work will help to further our understanding of the role mechanics may play in AAA formation, progression, and eventual rupture.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Goergen, Craig Jonathan |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Taylor, Charles A. (Charles Anthony) |
| Primary advisor | Tsao, Philip |
| Thesis advisor | Taylor, Charles A. (Charles Anthony) |
| Thesis advisor | Tsao, Philip |
| Thesis advisor | Dalman, Ronald L |
| Advisor | Dalman, Ronald L |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Craig J. Goergen. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Craig Jonathan Goergen
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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