Title:
Relationships between Mechanical Stress and Markers of Inflammation in Diseased Human Coronary Arteries

dc.contributor.advisor Vito, Raymond P.
dc.contributor.author Hallow, Karen Melissa en_US
dc.contributor.committeeMember Alexander Rachev
dc.contributor.committeeMember Hamid Garmestani
dc.contributor.committeeMember Guldberg, Robert E.
dc.contributor.committeeMember Rudolph Gleason
dc.contributor.committeeMember W. Robert Taylor
dc.contributor.department Mechanical Engineering en_US
dc.date.accessioned 2007-08-16T17:49:36Z
dc.date.available 2007-08-16T17:49:36Z
dc.date.issued 2007-07-05 en_US
dc.description.abstract Rupture of atherosclerotic plaque is one of the primary causes of death due to cardiovascular disease. The factors directing plaque progression to instability are poorly understood. It is well-known that arteries respond to changes in mechanical stress by remodeling, and that remodeling is mediated by the inflammatory response. Studies have shown that both mechanical stress and markers of inflammation are increased in the fibrous cap and shoulder regions of plaque, where rupture most often occurs. In this study we hypothesized that there are spatial relationships between the local mechanical environment and expression of markers of inflammation in atherosclerosis, and that these relationships are plaque-progression dependent. To test these hypotheses, we analyzed cross-sections at intervals along the length of human coronary atherosclerotic arteries. For each cross-section, a heterogeneous finite element model was developed to determine the spatial distribution of stress. In addition, novel techniques for quantifying inflammatory markers at high spatial resolution were used to determine the distributions of inflammatory markers. The distributions of stress and five markers of inflammation activated NF-kB, macrophages, MMP-1, nitrotyrosine, and microvessels - were then compared to determine whether spatial relationships exists. We demonstrated that the probability of activated NF-kB expression increases monotonically with increasing stress in all stages of plaque progression. This indicates that the relationship between mechanical stress and NF-kB activation is a player throughout the disease process. We found that the relationship between mechanical stress and macrophages is highly dependent on the state of plaque progression. In intermediate stages of progression macrophages increase with moderate stress but drop off again at very high stresses, while in the advanced stage macrophages continue to increase monotonically with stress. We found that MMP1 increases with stress in stages of progression where active remodeling is occurring, but decreases with stress in mature stable plaque. We found no relationship between mechanical stress and nitrotyrosine expression or microvessels. Taken together, these results support the role of mechanical stress in instigating and maintaining the inflammatory response, and help explain how mechanical input is able to direct the complex biological changes involved in remodeling. en_US
dc.description.degree Ph.D. en_US
dc.identifier.uri http://hdl.handle.net/1853/16211
dc.publisher Georgia Institute of Technology en_US
dc.subject Atherosclerosis en_US
dc.subject Plaque rupture en_US
dc.subject Inflammation en_US
dc.subject Nuclear factor - kappa B en_US
dc.subject Matrix metalloproteinase en_US
dc.subject Macrophages en_US
dc.subject Reactive oxygen species en_US
dc.subject Nitrotyrosine en_US
dc.subject Microvessels en_US
dc.subject Heterogeneous finite element model en_US
dc.subject.lcsh Strains and stresses en_US
dc.subject.lcsh Inflammation en_US
dc.subject.lcsh Coronary heart disease en_US
dc.subject.lcsh Atherosclerotic plaque en_US
dc.title Relationships between Mechanical Stress and Markers of Inflammation in Diseased Human Coronary Arteries en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Vito, Raymond P.
local.contributor.corporatename George W. Woodruff School of Mechanical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 94785f6f-1078-4c4b-b774-24282c6f0e55
relation.isOrgUnitOfPublication c01ff908-c25f-439b-bf10-a074ed886bb7
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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