Role of Proa(2)I collagen chains and collagen crosslinking in thoracic aortic biochemical integrity during aging using the OIM mouse model

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Role of Proa(2)I collagen chains and collagen crosslinking in thoracic aortic biochemical integrity during aging using the OIM mouse model

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/4397

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dc.contributor.advisor Phillips, Charlotte L. en
dc.contributor.author Pfeiffer, Brent J., 1975- en_US
dc.date.accessioned 2010-01-12T17:06:26Z
dc.date.available 2010-01-12T17:06:26Z
dc.date.issued 2006 en_US
dc.date.submitted 2006 Spring en
dc.identifier.other PfeifferB-042006-D5064 en_US
dc.identifier.uri http://hdl.handle.net/10355/4397
dc.description Title from title screen of research.pdf file (viewed on December 22, 2006). en_US
dc.description The 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.description Vita. en_US
dc.description "May 2006" en_US
dc.description Includes bibliographical references. en_US
dc.description Thesis (Ph. D.) University of Missouri-Columbia 2006. en_US
dc.description Dissertations, Academic -- University of Missouri--Columbia -- Biochemistry (Medicine). en_US
dc.description.abstract The 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.language.iso en_US en_US
dc.publisher University of Missouri--Columbia en_US
dc.subject.lcsh Collagen -- Metabolism en_US
dc.subject.lcsh Blood -- Circulation en_US
dc.subject.lcsh Aorta -- Mechanical properties en_US
dc.subject.mesh Collagen Type I -- metabolism en_US
dc.subject.mesh Aorta, Thoracic -- metabolism en_US
dc.subject.mesh Aorta, Thoracic -- physiopathology en_US
dc.subject.mesh Collagen Type I -- deficiency en_US
dc.subject.mesh Mice, Mutant Strains en_US
dc.subject.mesh Osteogenesis Imperfecta -- genetics en_US
dc.subject.mesh Osteogenesis Imperfecta -- metabolism en_US
dc.title Role of Proa(2)I collagen chains and collagen crosslinking in thoracic aortic biochemical integrity during aging using the OIM mouse model en_US
dc.type Thesis en_US
thesis.degree.discipline Biochemistry (Medicine) en_US
thesis.degree.grantor University of Missouri--Columbia en_US
thesis.degree.name Ph. D. en_US
thesis.degree.level Doctoral en_US
dc.identifier.merlin .b57475179 en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2006 Dissertations
dc.relation.ispartofcollection 2006 Freely available dissertations (MU)


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