The management and treatment of pelvic organ prolapse in the United States currently exceeds one billion dollars in costs annually. Elastin, the principle protein component of the elastic fiber, imparts vertebrate tissues such as the heart, lungs and skin with remarkable elasticity. The loss of elastin architecture and function is a pathological characteristic of a number of human degenerative and genetic disorders, and is believed to play a critical role in the vagina and in the pathophysiology of pelvic organ prolapse. The central hypothesis of this proposal is that vaginal birth degrades structural and dynamical properties of vaginal elastin compared to cesarean delivery. The objectives of this proposal are to quantitatively investigate the effects of modes of delivery on the structure of elastin of the vagina by pursuing two independent aims.
The first aim of the proposal is to measure the structural and dynamical properties of lysine, proline, valine, glycine and alanine rich segments of elastin of the vagina following various modes of delivery. A key characteristic of this protein that distinguishes it from other elastomers is that its function hinges on hydration only hydrated elastin retains its elasticity.
The second aim of the proposal is to measure the dynamics of water in vaginal elastin following various modes of delivery. This project will make use of nuclear magnetic resonance methods for these measurements. The proposal is interdisciplinary and encompasses biology, chemistry and physics. The methodology includes conventional carbon-13 nuclear magnetic resonance techniques that rely on magic angle spinning technology. In addition, the project will involve the use of non-commercial pulsed gradient fields, developed by the PI, to study time-dependent diffusion of water in elastin. The PI of the proposal is an Assistant Professor of Physics with significant expertise in nuclear magnetic resonance methodology and research experience in elastin. The PI was previously funded for four years under an NIH SC1 proposal. This proposal is a renewal application requesting four additional years of funding. This continued funding will assist the PI to transition to non-SCORE support by following a stepwise developmental plan provided in the biosketch.
The aim of this effort is to investigate the effects of mode of birth on elastin degradation in the vagina, using a murine model. The findings of this study will provide detailed insight into the role of elastin degradation, resulting from different modes of delivery, in pelvic organ prolapse. This innovative study will offer a paradigm for clinicians to measure exactly the effects of various interventions on vaginal elastin structure.
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