The role of tissue remodeling in mechanics and pathogenesis of abdominal aortic aneurysms.

Arterial walls can be regarded as composite materials consisting of collagen fibers embedded in an elastic matrix and smooth muscle cells. Remodeling of the structural proteins has been shown to play a significant role in the mechanical behavior of walls during pathogenesis of abdominal aortic aneurysms (AAA). In this study, we systematically studied the change in the microstructure, histology and mechanics to link them to AAA disease progression. We performed biaxial extension tests, second-harmonic generation imaging and histology on 15 samples from the anterior part of AAA walls harvested during open aneurysm surgery. Structural data were gained by fitting to a bivariate von Mises distribution and yielded the mean fiber direction and in- and out-of-plane fiber dispersions of collagen. Mechanical and structural data were fitted to a recently proposed material model. Additionally, the mechanical data were used to derive collagen recruitment points in the obtained stress-stretch curves. We derived 14 parameters from histology such as smooth muscle cell-, elastin-, and abluminal adipocyte content. In total, 22 parameters were obtained and statistically evaluated. Based on the collagen recruitment points we were able to define three different stages of disease progression. Significant differences in elastin content, collagen orientation and adipocyte contents were discovered. Nerves entrapped inside AAA walls pointed towards a significant deposition of newly formed collagen abluminally, which we propose as neo-adventitia formation. We were able to discriminate two types of remodeled walls with a high collagen content - potentially safe and possibly vulnerable walls with a high adipocyte content inside the wall and significant amounts of inflammation. The study yielded a hypothesis for disease progression, derived from the systematic comparison of mechanical, microstructural and histological changes in AAAs. STATEMENT OF SIGNIFICANCE: Remodeling of the structural proteins plays an important role in the mechanical behavior of walls during pathogenesis of abdominal aortic aneurysms (AAA). We analyzed changes in the microstructure, histology and biomechanics of 15 samples from the anterior part of AAA walls and, for the first time, linked the results to three different stages of disease progression. We identified significant differences in elastin content, collagen orientation, adipocyte contents, and also a deposition of newly formed collagen forming a neoadventitia. We could discriminate two types of remodeled walls: (i) potentially safe and (ii) possibly vulnerable associated with inflammation and a high amount of adipocytes.