The role of collagen in cardiac mechanics and adverse left ventricle remodeling post-myocardial infarction




Voorhees, Andrew

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Myocardial infarction (MI) occurs when the coronary arteries that supply blood to the myocardial tissue of the heart become blocked, triggering a dynamic wound healing response and eventually leading to the formation of a collagen rich scar tissue. The properties of the collagen network that forms dictate the mechanical behavior of the infarct tissue, which in turn alters the pumping function of the left ventricle (LV). However, little is known about how variations in the collagen network alter the function of the LV and contribute to differences in patient outcome. The goal of this dissertation is to clarify the mechanisms by which variation in the structural properties of the collagen network affect the mechanical properties of the infarct tissue and the pumping function of the LV through both computational and experimental approaches. The computational approach identified that a longitudinal alignment of collagen fibers in the infarct region is able to both maximize distension of the LV during diastolic filling and the contractile force generated by the healthy regions of the LV through the Frank-Starling mechanism. The experimental approach revealed a novel mechanism to reduce LV dilation by facilitating the assembly and cross-linking of collagen fibers through deletion of the gene for matrix metalloproteinase-9. This was the first study to quantify infarct mechanical properties in mice. This work opens up new areas for potential research and the findings may lead to the development of new diagnostic and therapeutic technologies.


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Adverse Left Ventricle Remodeling, Cardiac Mechanics, Collagen, Matrix Metalloproteinase-9, Myocardial Infarction



Biomedical Engineering