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dc.contributor.authorElhadj, Selimen_US
dc.date.accessioned2014-03-14T20:20:09Z
dc.date.available2014-03-14T20:20:09Z
dc.date.issued2001-12-10en_US
dc.identifier.otheretd-12112001-133454en_US
dc.identifier.urihttp://hdl.handle.net/10919/30041
dc.description.abstractThe overall focus of this dissertation is on how chronic shear stress alters the synthesis and secretion of important regulatory molecules by endothelial cells. Our hypothesis was that inclusion of chronic pulsatile shear stress in our model would lead to changes in endothelial cell release of regulatory molecules. We distinguished between high arterial shear stresses and low venous shear stresses and used static cell cultures as reference. The first part of this research thus entailed the complete characterization of the flow dynamics in our experimental biomechanical model. Cell stretching can have a physiological effect on endothelial cells; hence we implemented a laser based optical technique for real time strain measurement of the growth fibers used in our culture system, and found that no significant strains were occurring during shear treatment. After characterization of the mechanical environment of the cells, we focused the scope of our research on metabolism of proteoglycans and insulin-like growth factor-I (IGF-I) and related IGF binding proteins (IGFBPs) in bovine aortic endothelial cells cultured under chronic pulsatile shear. We found that shear stress increased the release of proteoglycans and significantly altered proteoglycans distribution. We also found that there was an inverse relationship between the shear level treatment used to obtain the purified proteoglycans from endothelial cells and their potency in inhibiting coagulation. IGF-I release and message (IGF-I mRNA) was decreased at high shear stress compared to low shear stress. Further, the levels found under shear were significantly greater than those observed in the static cell culture model. IGFBPs released were also significantly increased by shear. This research thus establishes a link between chronic pulsatile shear stress and the metabolism of both primary (IGF-I) and secondary (IGFBPs, proteoglycans) regulators of vascular cell activity. The improved realism of our experimental biomechanical model has proved to be a valuable tool in improving the relevance of this study to vascular research. Ultimately, this research calls for further investigation in the molecular mechanisms underlying the phenomenological effects documented, which may help in understanding fundamental aspects in cardiovascular disease and its link to hemodynamics but our work is an important first step.en_US
dc.publisherVirginia Techen_US
dc.relation.haspartdissertation5.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.subjectIGF-binding proteinsen_US
dc.subjectIGF-Ien_US
dc.subjectshear stressen_US
dc.subjectproteoglycansen_US
dc.subjectendothelial cellsen_US
dc.subjectstrainen_US
dc.titleChronic Shear Stress Effects on Endothelial Cell Responseen_US
dc.typeDissertationen_US
dc.contributor.departmentChemical Engineeringen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineChemical Engineeringen_US
dc.contributor.committeechairForsten-Williams, Kimberlyen_US
dc.contributor.committeememberVelander, William H.en_US
dc.contributor.committeememberGoldstein, Aaron S.en_US
dc.contributor.committeememberHoward, Rick Daleen_US
dc.contributor.committeememberAkers, Robert Michaelen_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-12112001-133454/en_US
dc.date.sdate2001-12-11en_US
dc.date.rdate2002-12-12
dc.date.adate2001-12-12en_US


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