All ETDs from UAB

Advisory Committee Chair

Dennis Pillion

Advisory Committee Members

Stephen Barnes

Rakesh Patel

Jeevan Prasain

J Michael Wyss

Document Type

Dissertation

Date of Award

2008

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Despite medical advances in both drug therapy and surgical techniques, Americans mostly die from heart disease. Many belong to the low- and middle-class families who do not have sufficient access to medical care due to its high costs. An alternative is the development of healthier lifestyles such as diet which may play a positive role in chronic disease management. Epidemiological and migratory studies suggest that soy plays a pivotal role in the decreased incidence of heart disease in East Asian countries, such as China, Japan, and Korea. The role of soy in cardiovascular disease progression has been the subject of research. Possible mechanisms include modulation of endothelial cell function, alteration in platelet reactivity, inflammatory cell function, and scavenging of reactive oxygen and nitrogen species. These studies have focused on the role of isoflavones as the component of soy that acts on these cellular processes. Despite extensive research, there remains conflict as to whether the isoflavones are beneficial. This could be due to the use of the aglycones in cell culture experiments that are not representative of the forms in plasma. Typically, isoflavones exist in their glucuronidated forms in plasma. Previous studies have shown that the isoflavones can be modified by activated neutrophils to produce chlorinated products. These products have greater anti-oxidant activity in low density lipoprotein (LDL) model systems of atherosclerosis. In order to translate these in vitro ii studies to in vivo models, it became necessary to understand the pharmacokinetics of the newly formed chlorinated isoflavones. This dissertation aims to attain a greater understanding of the isoflavones present during the inflammatory component of atherosclerosis.

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