Date of Award
2016
Document Type
Open Access Dissertation
Department
Biomedical Engineering
First Advisor
Susan M. Lessner
Abstract
Failure of atherosclerotic plaques can lead to potentially life threatening clinical events such as myocardial infarction (MI), stroke, or transient ischemic attack (TIA). The most frequently described plaque failure mechanism is tensile rupture of the fibrous cap; however, often during angioplasty another plaque failure mechanism occurs in which the atherosclerotic plaque separates from the internal elastic lamina (IEL). This study aims assess the material strength of atherosclerotic lesions using mechanical concepts.
To assess likelihood of plaque dissection at the vessel wall, adhesion strength was assessed in both mouse and human specimens using plaque delamination experiments. Measuring plaque adhesion in transgenic mouse models can be useful in understanding the contributions to plaque adhesion from specific proteins. Comparing these results to similar delamination experiments in human plaques aids in understanding the similarities between mechanical properties of plaques in the two species.
To further understand adhesive failure at the plaque-IEL interface, the contributions of adhesive proteins to the mechanical strength of the plaque-IEL interface were investigated. The results from a novel semi-quantitative plaque immunoblotting technique and measurements of adhesive strength of thin protein films combine to provide an estimate of the adhesive strength of relevant matrix proteins at approximate ex vivo concentrations. The adhesion strength in thin protein films is much lower than that determined from in situ plaque adhesion experiments and suggests that bridging fibers, rather than adhesive proteins, are likely to be responsible for the adhesive strength of the plaque-IEL interface.
In addition to plaque adhesion strength, plaque stability was also assessed by investigating the resistance to tensile rupture of the fibrous caps in human carotid endarterectomy specimens. Mechanical strength of fibrous caps was assessed during failure by calculating crack tip opening displacement (CTOD) and stress in the uncracked segment (UCS) in miniature single edge notched tensile (MSENT) specimens. The results show that fibrous caps with greater collagen content exhibit more brittle behavior and fail at a higher stress and a smaller CTOD than those with a lower collagen content, which exhibit a more ductile response. Knowledge of the collagen content in the fibrous cap prior to surgical intervention could predict the mechanical response of the fibrous cap and aid in determining the optimal treatment plan.
Fracture toughness was used to assess plaque resistance to two different failure mechanisms: 1) plaque delamination at the plaque-IEL interface and 2) tensile rupture of the fibrous cap. Collagen is a vital structural component of atherosclerotic plaques and is crucial in determining the mechanical response of fibrous caps. Fibrillar forms of collagen, such as collagen I, or other fibrillar proteins, such as fibrillin-1, are likely responsible for the mechanical strength of the plaque-IEL interface.
Rights
© 2016, Lindsey A. Davis
Recommended Citation
Davis, L. A.(2016). A Mechanical Approach to the Characterization of Material Failure of Atherosclerotic Lesions. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/3547