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dc.contributor.advisorSeye, Cheikh I.eng
dc.contributor.advisorWeisman, Gary A.eng
dc.contributor.authorYu, Ningpu, 1979-eng
dc.date.issued2007eng
dc.date.submitted2007 Falleng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionTitle from title screen of research.pdf file (viewed on March 12, 2008)eng
dc.descriptionVita.eng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2007.eng
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Biochemistry (Agriculture)eng
dc.description.abstractExtracellular nucleotides act on P2 receptors to regulate vascular tone. Large amounts of extracellular nucleotides are released at the sites of tissue injury and may play an important role in the vascular inflammation. In vascular injury models, P2Y₂ mRNA was significantly up-regulated. Activation of up-regulated P2Y₂ receptors in the injured artery increased monocyte/macrophage infiltration and intimal hyperplasia. In this dissertation, we showed that activation of the P2Y₂ receptor modulates the expression of VCAM-1 in vascular endothelial cells that is important for monocyte recruitment. We report here that P2Y₂ receptor-induced VCAM-1 expression is mediated by rapid tyrosine phosphorylation of VEGFR-2 in HCAEC. RNA interference (RNAi) targeting of VEGFR-2 expression or inhibition of VEGFR-2 tyrosine kinase activity abolished P2Y₂ receptor-mediated VCAM-1 expression. We also discovered that the P2Y₂ receptor is linked to the cytoskeleton through direct interaction with the actin-binding protein filamin A (FLNa), which is a large protein of 280 kD and serves as a cross-linker of actin polymers and as a scaffolding protein for various signaling molecules. This interaction was mapped to the C-terminal tail of the P2Y2 receptor (amino acids 322 to 333) and is required for FLNa phosphorylation, spreading and migration of smooth muscle cells induced by extracellular nucleotides. These results encourage drug design targeting the P2Y₂ receptor as a means to prevent and/or treat arterial disease.eng
dc.identifier.merlinb66635809eng
dc.identifier.oclc314398562eng
dc.identifier.urihttps://hdl.handle.net/10355/4664
dc.identifier.urihttps://doi.org/10.32469/10355/4664eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.sourceSubmitted by University of Missouri--Columbia Graduate School.eng
dc.subjectfilamin Aeng
dc.subject.lcshVasculitiseng
dc.subject.lcshChemotaxiseng
dc.subject.lcshEndothelinseng
dc.subject.lcshPhosphorylationeng
dc.titleThe role of P2Y₂ nucleotide receptors in vascular inflammationeng
dc.typeThesiseng
thesis.degree.disciplineBiochemistry (Agriculture) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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