| Aneurysms are devastating. Most aneurysms are asymptomatic, and AAA rupture is typically fatal, causing pain, paralysis, loss of function, and death. With aneurysm formation, elastin degrades, the vessel dilates, media thins, and the vessel stiffens. Changes in vessel composition and function are well known. However, lack of three-dimensional data at micro- and nano-scales has limited our understanding of microstructural changes in the aortic media. We applied novel electron and confocal microscopy techniques to produce three-dimensional volumes of aortic medial micro- and nano-structure from normal and diseased rat abdominal aortas.;Images of the normal rat aorta reveal complex and organized structure. Nearly 1/3rd of elastin exists between lamellae as a dense network of interlamellar elastin fibers (IEFs) and thick radial elastin struts. Smooth muscle cells (SMCs) extend throughout interlamellar space, cytoplasmic ends abut IEFs, and nuclei tilt 19° toward top and bottom lamellae. Collagen fiber bundles align parallel to each other within radial layers. All 3 primary mural constituents orient predominantly in the circumferential direction.;Aneurysms present a paradox...Aneurysms are comprised of increased amounts of collagen, an extremely strong and stiff material. Yet, aneurysms eventually rupture under normal physiological conditions. We used a rat elastase-infusion model of aneurysm to resolve this paradox. Results show that elastin loss disturbs SMC and collagen remodeling. Loss of SMC attachment to elastin results in SMC apoptosis. Collagen remodels under increased stress and strain, resulting in longer and weaker collagen matrices. Repeated remodeling and repair cycles throughout aneurysm development accumulate into macroscopic vessel enlargement and weakening. Localized failures accumulate and tissue weakens until macroscopic failure transpires at physiological stresses. |
