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dc.contributor.advisorBrown, Michael D.
dc.creatorSturgeon, Katie
dc.date.accessioned2020-11-03T15:33:52Z
dc.date.available2020-11-03T15:33:52Z
dc.date.issued2011
dc.identifier.other864885802
dc.identifier.urihttp://hdl.handle.net/20.500.12613/2474
dc.description.abstractPurpose: Translational research characterizing endothelial dysfunction and the progression of cardiovascular disease (CVD) is necessary for understanding the complex nature of multi-factorial diseases. Perhaps more important though, is understanding the compensatory and adaptive processes associated with regression of diseases and chronic oxidative stress. Vascular endothelial growth factor (VEGF) is an important protein in endothelial health and nitric oxide (NO) production. The purpose of this research was to examine changes in VEGF-mediated endothelial nitric oxide synthase (eNOS) activity under conditions of oxidative stress both in vivo and in vitro. Methods: The oxidative stress relationship involving plasma VEGF, NO, and hydrogen peroxide (H2O2) was assessed in sedentary, pre-hypertensive African American participants both (n=48) before and following (n=22) 6 months of aerobic exercise training (AEXT). In vitro, H2O2 exposure along with atherogenic, 4 dyne/cm2, and athero-protective, 20 dyne/cm2, levels of laminar shear stress (LSS) were used to characterize VEGF-mediated eNOS activity to gain insights into physiological signaling. Results: At baseline, VEGF levels increased with increasing blood pressure (BP) level while NO levels decreased from normotensive to hypertensive participants. H2O2 levels also trended upward with increasing BP level, and in vitro H2O2 was observed to decrease VEGF-mediated eNOS activity in a dose dependent manner. Following AEXT, participants were divided into groups relative to their BP change following the intervention. Participants that decreased their BP level demonstrated a decrease in VEGF and H2O2 level. In addition, following 24 hrs of LSS at 20 dyne/cm2, VEGF-mediated eNOS activity and VEGFR2 protein expression was significantly lower compared to 24 hrs of LSS at 4 dyne/cm2. Discussion: Increased circulating levels of VEGF in vivo may be a compensatory mechanism. Endothelial dysfunction and progressive CVD may trigger such compensation. The adaptive response to exercise for its BP-lowering effects is systemic and encompasses many changes. These beneficial adaptations have likely alleviated the compensatory mechanism of elevated VEGF levels seen at baseline. Indeed, following 24 hrs of an athero-protective LSS level, VEGF-mediated eNOS activity was significantly lower compared to 24 hr of LSS at an atherogenic level. The difference in VEGF-mediated eNOS activity may be due, in part, to the decrease in VEGFR2 protein expression we observed under an athero-protective LSS level.
dc.format.extent110 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectKinesiology
dc.subjectBiology, Molecular
dc.subjectPhysiology
dc.subjectEnos
dc.subjectExercise
dc.subjectHydrogen Peroxide
dc.subjectHypertension
dc.subjectOxidative Stress
dc.subjectVegf
dc.titleIn Vivo and In Vitro Interactions of Oxidative Stress and Laminar Shear Stress on Vascular Endothelial Growth Factor-Mediated Endothelial Nitric Oxide Synthase Activity
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberRizzo, Victor
dc.contributor.committeememberPark, Joon Young
dc.contributor.committeememberKendrick, Zebulon V.
dc.contributor.committeememberPatterson, Freda
dc.description.departmentKinesiology
dc.relation.doihttp://dx.doi.org/10.34944/dspace/2456
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
refterms.dateFOA2020-11-03T15:33:52Z


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