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dc.contributor.authorKim, Paul Hyunchulen_US
dc.date.accessioned2014-03-14T20:33:57Z
dc.date.available2014-03-14T20:33:57Z
dc.date.issued2010-04-14en_US
dc.identifier.otheretd-04202010-141220en_US
dc.identifier.urihttp://hdl.handle.net/10919/31798
dc.description.abstractCardiovascular disease (CVD) including atherosclerosis is the leading cause of illness and death in the United States. The American Heart Association indicated that an estimated 81,100,000 American adults have one or more types of CVD and the estimated direct and indirect cost of CVD for 2010 is $503.2 billion, which is $27.9 billion more than last year. Although the exact cause of this disease remains unsolved, previous studies have demonstrated that pro-oxidative and pro-inflammatory pathways in vascular endothelium play a critical role in early pathological events of atherosclerosis. However, the detailed molecular signaling mechanisms underlying this process are not yet completely understood. Recently, the role of interleukin-4 (IL-4) in atherogenesis became controversial and gained attention. IL-4 is a pleiotropic immunomodulatory cytokine secreted by T-helper 2 (Th2) lymphocytes, eosinophils, and mast cells. It was traditionally believed to be an anti-inflammatory cytokine. Increasing evidence, however, has suggested that IL-4 contributes to the initiation and progression of atherosclerosis by oxidative stress-mediated up-regulation of pro-inflammatory mediators such as vascular cell adhesion moledule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in vascular endothelium. 5-Lipoxygenase (5-LOX) is one of the key sources that generate reactive oxygen species (ROS) via metabolic pathways of arachidonic acid. Although 5-LOX has been implicated in the development of atherosclerosis, it remains unclear whether 5-LOX-mediated ROS generation is associated with IL-4-induced MCP-1 expression in vascular endothelium. The present study was focused on the oxidative mechanisms by which IL-4 induces vascular inflammation as well as how 5-LOX is involved in this process. The results showed that IL-4 significantly up-regulates mRNA and protein expression of MCP-1 in vascular endothelium. In addition, DHE and DCF fluorescence staining demonstrated that IL-4 increases ROS production in human vascular endothelial cells. We have also provided the first novel evidence that 5-LOX, one of the enzymes associated with arachidonic acid metabolism, is responsible for the IL-4-induced ROS generation and MCP-1 expression in human vascular endothelial cells.en_US
dc.publisherVirginia Techen_US
dc.relation.haspartKim_Paul_T_2010.pdfen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectAtherosclerosisen_US
dc.subjectInflammationen_US
dc.subjectVascular Endotheliumen_US
dc.subjectInterleukin-4en_US
dc.subject5-Lipoxygenaseen_US
dc.titleRole of 5-Lipoxygenase in Interleukin-4-Induced Oxidative Stress and Inflammation in Vascular Endotheliumen_US
dc.typeThesisen_US
dc.contributor.departmentBiomedical and Veterinary Sciencesen_US
dc.description.degreeMaster of Scienceen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiomedical and Veterinary Sciencesen_US
dc.contributor.committeechairLee, Yong Wooen_US
dc.contributor.committeememberTanko, James M.en_US
dc.contributor.committeememberHuckle, William R.en_US
dc.contributor.committeememberDuncan, Susan E.en_US
dc.contributor.committeememberAhmed, S. Ansaren_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-04202010-141220/en_US
dc.date.sdate2010-04-20en_US
dc.date.rdate2010-05-21
dc.date.adate2010-05-21en_US


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