Title:
Modulating the Functional Contributions of c-Myc to the Human Endothelial Cell Cyclic Strain Response

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dc.contributor.advisor McIntire, Larry V.
dc.contributor.author Hurley, Nicole Elizabeth en_US
dc.contributor.committeeMember Marion Sewer
dc.contributor.committeeMember Ray Vito
dc.contributor.committeeMember Suzanne Eskin
dc.contributor.committeeMember Todd McDevitt
dc.contributor.department Mechanical Engineering en_US
dc.date.accessioned 2008-02-07T18:42:30Z
dc.date.available 2008-02-07T18:42:30Z
dc.date.issued 2007-11-09 en_US
dc.description.abstract With each heartbeat, major arteries experience circumferential expansion due to internal pressure changes. This pulsatile force is called cyclic strain and has been implicated in playing a pivotal role in the genetic regulation of vascular physiology and pathology. This dissertation investigates the hypothesis that in human umbilical vein endothelial cells (HUVEC), pathological levels of cyclic strain activate the c-Myc promoter, leading to c-Myc transcription and downstream gene induction. To determine expression and time-dependency of c-Myc in HUVEC, mRNA and protein expression of c-Myc under physiological (6-10% cyclic strain) and pathological conditions (20% cyclic strain) were studied. Both c-Myc mRNA and protein expression increased more than three-fold in HUVEC (P4-P5) cyclically-strained at 20%. This expression occurred in a time-dependent manner, peaking in the 1.5-2 hour range and falling to basal levels by 3 hours. Subsequently, the mechanism of c-Myc transcription was investigated by using specific inhibitors to modulate c-Myc transcriptional activation. These compounds, obtained from the University of Arizona Cancer Center, attenuated cyclic-strain-induced c-Myc transcription by about 50%. Having established this reduction in expression, it was investigated how these effects modulate downstream genes that are regulated by c-Myc. The results indicate that direct targeting of the c-Myc promoter may decrease stretch-induced gene expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and heat shock protein 60 (HSP60). These findings may help in the development of a novel therapeutic opportunity in vascular diseases. en_US
dc.description.degree Ph.D. en_US
dc.identifier.uri http://hdl.handle.net/1853/19822
dc.publisher Georgia Institute of Technology en_US
dc.subject Drug-eluting stent en_US
dc.subject Atherosclerosis en_US
dc.subject Stretching en_US
dc.subject.lcsh Blood-vessels Diseases
dc.subject.lcsh Cardiovascular system Diseases
dc.subject.lcsh Strains and stresses
dc.subject.lcsh Myc oncogenes
dc.title Modulating the Functional Contributions of c-Myc to the Human Endothelial Cell Cyclic Strain Response en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor McIntire, Larry V.
local.contributor.corporatename George W. Woodruff School of Mechanical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 22b48b80-ffb5-4b9d-82f9-be63cbe3d87d
relation.isOrgUnitOfPublication c01ff908-c25f-439b-bf10-a074ed886bb7
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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