Activation by mechanical stress and regional changes of transforming growth factor beta signaling in the pathogenesis of thoracic aortic aneurysms : a dissertation /
| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2013]
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| Subjects: |
| Abstract: | ABSTRACT: Remodeling of blood vessels in patients with Marfan Syndrome (MFS), a disorder caused by mutations of Fibrillin-1 (Fbn-1), is inadequate because it lacks spatial and temporal regulation. MFS patients consistently develop thoracic aortic aneurysms (TAAs) which are characterized by degradation of the medial ECM and loss of smooth muscle cells (SMC) as a result of altered structural components and dysregulation of regulatory pathways, specifically Transforming growth factor beta (TGF[beta]). Our first goal was to determine if changes in vascular wall stresses play a key role in the regulation of signaling through the TGF[beta] pathway in blood vessels. Collectively, these results suggest that mechanical stress can not only lead to activation of TGF[beta] but also alter signaling through the Smad pathway. Our second goal was to examine the spatial and temporal expression alterations of vascular genes in a MFS mouse model and furthermore to examine the different roles of Smad 2/3 in those genes. The observed change in TGF[beta] signaling in aging and gender, in regions of the aorta, could be a consequence of elastic fiber fragmentation, increased vascular wall stiffness and alterations in TGF[beta] through the Smads. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy Februrary 2013." Approved as to style and content by: Emily Wilson, Farida Sohrabji, Warren E. Zimmer, Brett Mitchell, Harris J. Granger. |
| Physical Description: | xi, 120 leaves : illustrations (mostly color) ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 101-116). |