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dc.contributor.advisorRizzo, Victor
dc.contributor.advisorEguchi, Satoru
dc.creatorBoyer, Michael
dc.date.accessioned2020-08-25T19:55:08Z
dc.date.available2020-08-25T19:55:08Z
dc.date.issued2020
dc.identifier.urihttp://hdl.handle.net/20.500.12613/284
dc.description.abstractEndothelial dysfunction, present in most cardiovascular disease, results in up-regulation of inflammatory adhesion molecules/cytokines, increases in vascular permeability, and decreased vasoprotective factors leading to vascular dysfunction. A novel means of communication between almost all cells are small vesicles containing biologically active proteins, nucleic acids, and lipids known as extracellular vesicles. Despite the advances in cardiovascular biology, the role of extracellular vesicles between endothelial cells and cells of vascular wall are underexplored. Therefore, we hypothesized that endothelial activation results in the release of pro-inflammatory vesicles that initiate inflammatory remodeling of vascular smooth muscle cells of the aorta. Extracellular vesicles were released from both endothelial cells and vascular smooth muscle cells with characteristic size, shape, and content. However, serum-free collection in endothelial cells resulted in endothelial activation of cell in culture and resulted in altered function in vascular smooth muscle cells, characterized by increased monocyte adhesion, altered protein synthesis/signal transduction, and signs of pro-senescent features. These effects were not recapitulated in any combination of endothelial-vascular smooth muscle cell extracellular vesicle communication. Unbiased mass spectroscopy of vascular smooth muscle cell treated with serum-free endothelial vesicles identified several proteins significantly up- regulated, including high mobility group box 1 and 2. Pharmacologic and genetic inhibition of these molecules significantly attenuated NF-kB activation, VCAM-1 expression, and monocyte adhesion. In summation, we suggest a new axis through which endothelial activation releases vesicles that skew the function of vascular smooth muscle cells to phenotype characterized by inflammatory properties through up-regulation of high mobility group box proteins 1 and 2. This highlights the importance of extracellular vesicles as a novel communication method between cells of the vasculature and how alterations in the host cell function may change the function of these vesicles.
dc.format.extent208 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.subjectPhysiology
dc.subjectCell Biology
dc.subjectExtracellular Vesicles
dc.subjectVascular Biology
dc.titleEXTRACELLULAR VESICLES IN THE VASCULATURE: NOVEL MEANS OF COMMUNICATION DURING VASCULAR INSULT
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberTouyz, Rhian M.
dc.contributor.committeememberKishore, Raj
dc.contributor.committeememberAutieri, Michael V.
dc.contributor.committeememberScalia, Rosario
dc.description.departmentBiomedical Sciences
dc.relation.doihttp://dx.doi.org/10.34944/dspace/268
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
dc.identifier.proqst14151
dc.creator.orcid0000-0001-7080-8767
dc.date.updated2020-08-18T19:04:38Z
refterms.dateFOA2020-08-25T19:55:09Z
dc.identifier.filenameBoyer_temple_0225E_14151.pdf


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