Title:
Mechanical Strain-Mediated Syndecan Regulation and Its Effects on Adhesion of Vascular Smooth Muscle Cells

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dc.contributor.advisor Chaikof, Elliot L.
dc.contributor.advisor García, Andrés J.
dc.contributor.author Julien, Mathéau A. en_US
dc.contributor.committeeMember Anew P. Kowalczyk
dc.contributor.committeeMember Taylor, W. Robert
dc.contributor.committeeMember Galis, Zorina S.
dc.contributor.department Biomedical Engineering en_US
dc.date.accessioned 2005-07-28T19:35:09Z
dc.date.available 2005-07-28T19:35:09Z
dc.date.issued 2005-01-19 en_US
dc.description.abstract An injured vascular system has a substantial impact on an individuals overall health, and an understanding of the mechanisms that underlie blood vessel pathophysiology is required for the development of rational and effective treatment strategies. The phenotypic modulation of smooth muscle cells (SMC) during vascular injury, characterized by altered adhesion, migration and synthetic behavior, plays an important role in the eventual outcome. Specifically, the ability of SMCs to adhere to and remodel their extracellular environment via regulation of the syndecan class of cell adhesion molecules dictates the response of the vascular wall to local injury. The effect of in vitro syndecan-4 regulation on SMC adhesion was investigated through the use of a glass microsphere centrifugation assay, and an antisense-mediated reduction in gene expression was found to correlate with decreased adhesive strength. Regulation of syndecan-1, syndecan-2, and syndecan-4 gene expression was observed experimentally by mechanical strain of SMCs. Using real-time polymerase chain reaction (PCR), the kinetics of both static and cyclic mechanical strain were found to modify the gene expression in a time and strain magnitude-dependent manner unique to each syndecan. In particular, the responses of syndecan-4 were acute, but transient, while the evolution of syndecan-1 and syndecan-2 regulation was delayed by comparison. Mechanical strain also modulated syndecan-4 protein expression and ectodomain shedding, as measured by Western immunoblotting, and this effect was found, through selective inhibition, to be at least in part dependent on mitogen-activated protein (MAP) kinase signaling. In particular, intact extracellular signal-regulated MAP kinase (ERK) 1/2 and c-Jun NH2-terminal kinase / stress-activated protein kinase (JNK/SAPK) signaling pathways were found to be required for the observed strain-induced shedding. These findings offer a better understanding of syndecan function in response to mechanical strain and suggest potential new mechanisms by which physical forces may modulate vascular SMC behavior and regulation during normal physiology, pathologic conditions, and engineered arterial substitute development. en_US
dc.description.degree Ph.D. en_US
dc.format.extent 4558342 bytes
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/7007
dc.language.iso en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject Vascular graft en_US
dc.subject Mitogen activated protein kinase
dc.subject Tissue engineering
dc.subject Ectodomain shedding
dc.subject Cell adhesion
dc.subject Smooth muscle
dc.subject Cyclic strain
dc.subject Cyclic stress
dc.subject Biomechanics
dc.subject Syndecan
dc.subject Heparan sulfate proteoglycan
dc.subject.lcsh Vascular smooth muscle en_US
dc.subject.lcsh Blood-vessels Pathophysiology en_US
dc.subject.lcsh Cell physiology en_US
dc.subject.lcsh Strains and stresses en_US
dc.title Mechanical Strain-Mediated Syndecan Regulation and Its Effects on Adhesion of Vascular Smooth Muscle Cells en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename College of Engineering
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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