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作者 Hallow, Karen Melissa
書名 Relationships between mechanical stress and markers of inflammation in diseased human coronary arteries
國際標準書號 9780549110163
book jacket
說明 249 p
附註 Source: Dissertation Abstracts International, Volume: 68-07, Section: B, page: 4635
Adviser: Raymond P. Vito
Thesis (Ph.D.)--Georgia Institute of Technology, 2007
Rupture of atherosclerotic plaque is the primary cause 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 tend to be increased in the fibrous cap and shoulder regions of atherosclerotic 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 regular intervals along the length of human coronary atherosclerotic arteries. For each cross-section, a 2D heterogeneous finite element model was developed to determine the spatial distribution of stress in the cross-section. In addition, novel techniques for quantifying inflammatory markers at high spatial resolution were used to determine the distributions of a set 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 a spatial relationship 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
School code: 0078
DDC
Host Item Dissertation Abstracts International 68-07B
主題 Engineering, Biomedical
Engineering, Mechanical
0541
0548
Alt Author Georgia Institute of Technology
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