Theses and Dissertations
Issuing Body
Mississippi State University
Advisor
Warnock, James N.
Committee Member
McCarthy, Fiona
Committee Member
Liao, Jun
Committee Member
Burgess, Shame
Committee Member
Elder, Steven
Date of Degree
12-11-2009
Document Type
Dissertation - Open Access
Major
Biomedical Engineering
Degree Name
Doctor of Philosophy
College
James Worth Bagley College of Engineering
Department
Department of Agricultural and Biological Engineering
Abstract
Calcific aortic valve disease (CAVD) is the most common cause of aortic valve failure and replacement in the elderly population, affecting 25% of the population over 65 years of age. Current pharmacological approaches for preventing the onset and progression of calcific aortic valve disease have not shown consistent benefits in clinical studies. Differentiation of valvular interstitial cells (VICs) into osteoblast–like cells is an integral step in the calcification process. Although clinical evidence suggests hypertension as a potential candidate contributing to the development of CAVD, the underlying molecular mechanisms that cause de-differentiation remain unclear. The present study investigates the role of elevated cyclic pressure in modulating osteoblast differentiation pathways in VICs in vitro. We used a combination of systems biology modeling and pathway-based analyses to identify novel genes and molecular mechanisms that are activated in valve tissue during exposure to elevated pressure conditions. Our results show that elevated pressure induces a gene expression pattern in valve tissue that is considerably similar to that seen in CAVD, underlining the key role of hypertension as an initiating factor in the onset of pathogenesis. In addition, our analysis revealed a set of genes that was not previously known to be regulated in valve tissue in a pressure dependent manner. Currently, the molecular mechanisms involved in CAVD and their associations with changes in local mechanical environment are poorly understood, and thus a better understanding of the cell based process mediating CAVD progression will improve our ability to develop potential medical therapies for this disease.
URI
https://hdl.handle.net/11668/17494
Recommended Citation
Gamez, Carol Andrea Pregonero, "Osteogenic Regulatory Mechanisms Activated By Pressure In Aortic Heart Valve" (2009). Theses and Dissertations. 3420.
https://scholarsjunction.msstate.edu/td/3420
Comments
OPN||RUNX2||Angiotensin II||ALP||Cyclic Pressure||Valvular Interstitial Cells||BMP-7||SMAD1