Improved methods for phenotypic characterization of rat collecting lymphatics and their application in evaluating the biological determinants of lymphatic contractility : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2009]
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| Subjects: |
| Abstract: | ABSTRACT: Collecting lymphatic vessels exhibit contractile patterns that are both necessary and sufficient to generate lymph flow, play significant roles in both immune cell transport and dietary lipid absorption, and are likely the primary source of dysfunction in the most prolific disease of the lymphatic system, lymphedema. Despite these observations, our knowledge and understanding of the molecular and biological determinants of collecting lymphatic vessel physiology remains limited. To address this, we have developed and/or applied new strategies to unravel the collecting lymphatic vessel phenotype. Through the application of microarray and quantitative PCR technologies, we constructed a database of mRNA profiles encompassing arterial, venous, and lymphatic lineages in two different tissue beds and identified gene sets related to intracellular signaling, microtubular organization and function, immune function, and RNA handling as representing major transcriptional differences between blood and lymphatic vessels. To extend collecting lymphatic expression profiling to the protein level, we developed a simplified immunohistochemistry protocol for rapid protein expression screening in rat mesenteric collecting lymphatics and identified vanilloid receptor 1 as consistently displaying elevated expression levels in lymphatic smooth muscle cells relative to vascular smooth muscle cells. Finally, we have developed a new software tool to provide automated analysis of lymphatic contractile events from lymphatic diameter traces and utilized this tool to evaluate the effects of natriuretic peptides on rat lymphatic contractility. We show that atrial, brain, and C-type natriuretic peptides all significantly increase phasic contractile frequency and reduce diastolic diameter in mesenteric collecting lymphatics despite the presumed activation of a cGMP signaling cascade typically associated with contractile inhibition thus revealing a possibly new intracellular signaling mechanism in lymphatic smooth muscle. Collectively, the methods and data will contribute to our further understanding of the collecting lymphatic vessel phenotype and its role in health and disease. |
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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 August 15 2009." Approved as to style and content by: Mariappan Muthuchamy, David C. Zawieja, Emily Wilson, Anatoliy A. Gashev, Harris J. Granger. |
| Physical Description: | xii, 169 leaves : illustrations (some color) ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 131-155). |