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dc.contributor.advisorPhillips, Charlotte L.en
dc.contributor.authorPfeiffer, Brent J., 1975-en_US
dc.date.issued2006eng
dc.date.submitted2006 Springen
dc.descriptionTitle from title screen of research.pdf file (viewed on December 22, 2006).en_US
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.en_US
dc.descriptionVita.en_US
dc.description"May 2006"en_US
dc.descriptionIncludes bibliographical references.en_US
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2006.en_US
dc.descriptionDissertations, Academic -- University of Missouri--Columbia -- Biochemistry (Medicine).en_US
dc.description.abstractThe extracellular matrix (ECM) is an important constituent for a variety of tissues including vascular tissue in which the ECM maintains aortic wall integrity. An important component of vascular tissue ECM is type I collagen. Type I collagen is normally a molecule composed of three collagen chains of which two are the same chain [proa1(I)] and one is distinctly different [proa2(I)]. The focus of this dissertation is to examine the role of the proa2(I) chain in determining thoracic aorta integrity and how the thoracic aortic integrity changes with age. To assess the role of proa2(I) chains we used a mouse model, termed 'oim', that produces only proa1(I) chains and evaluated thoracic aortas of our mouse model at 3, 8, and 18 months old of age. We evaluated thoracic aortic strength, stiffness, ECM content, ECM gene expression, and collagen crosslinking at each age point. Oim mice exhibited reduced aortic strength and stiffness at each age group and exhibited increased aortic strength and stiffness at 18 months of age compared to 3 months of age. Oim mice also exhibited reduced aortic collagen content, while other aortic ECM components were unchanged. However, aortic collagen content was significantly increased at 8 and 18 months of age as compared to 3 months of age. Aortic ECM gene expression demonstrated reduced expression at 18 months of age as compared to 3 months of age. In addition, oim aortas demonstrated increased collagen crosslinks at each age group, while the ratio of collagen crosslinking remained the same at each age group. Our results demonstrate that proa2(I) collagen is central for proper aortic strength and stiffness even in the presence of increased collagen crosslinking and increasing collagen content of homotrimeric type I collagen with age. This study suggests that fibrils composed of homotrimeric type I collagen are inherently weaker than fibrils composed of heterotrimeric type I collagen.en_US
dc.identifier.merlin.b57475179en_US
dc.identifier.otherPfeifferB-042006-D5064en_US
dc.identifier.urihttp://hdl.handle.net/10355/4397
dc.publisherUniversity of Missouri--Columbiaen_US
dc.relation.ispartofcollection2006 Freely available dissertations (MU)
dc.relation.ispartofcommunityUniversity of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2006 Dissertations
dc.subject.lcshCollagen -- Metabolismen_US
dc.subject.lcshBlood -- Circulationen_US
dc.subject.lcshAorta -- Mechanical propertiesen_US
dc.subject.meshCollagen Type I -- metabolismen_US
dc.subject.meshAorta, Thoracic -- metabolismen_US
dc.subject.meshAorta, Thoracic -- physiopathologyen_US
dc.subject.meshCollagen Type I -- deficiencyen_US
dc.subject.meshMice, Mutant Strainsen_US
dc.subject.meshOsteogenesis Imperfecta -- geneticsen_US
dc.subject.meshOsteogenesis Imperfecta -- metabolismen_US
dc.titleRole of Proa(2)I collagen chains and collagen crosslinking in thoracic aortic biochemical integrity during aging using the OIM mouse modelen_US
dc.typeThesisen_US
thesis.degree.disciplineBiochemistry (Medicine)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoralen_US
thesis.degree.namePh. D.en_US


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