| Start Date: | 11/29/2016 | Start Time: | 10:00 AM |
| End Date: | 11/29/2016 | End Time: | 12:00 PM |
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Event Description
BIOMED PhD Research Proposal
Title:
Hypoxic Nitrite Reduction to Nitric Oxide (NO): A Computational Modeling Approach
Speaker:
Yien Liu, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Advisor:
Dov Jaron, PhD, Calhoun Distinguished Professor of Engineering in Medicine, School of Biomedical Engineering, Science and Health Systems
Abstract:
Nitric oxide (NO) is a powerful paracrine signaling molecule that plays a critical role in regulating blood vessel tone and vascular homeostasis. Hypoxic and ischemic conditions lead to deficiencies in endothelial NO production, which has been implicated in many cardiovascular and neurodegenerative diseases. Nitrite has been shown to act as a storage pool for NO that is inactive in normoxia, but enzymatically reduced in hypoxia to restore lost NO. Recent experiments have identified a growing number of therapeutic applications of nitrite, such as reduction of hypertension and mitigation of ischemia/reperfusion injury, but the nitrite reduction mechanisms involved are not well understood. There is a need for mathematical modeling to characterize these pathways. Three computational studies are proposed to systematically analyze the role of nitrite as a hypoxic NO-producing mechanism in various organ and tissue systems.
First, we propose to determine how nitrite infused into the blood paradoxically induces vasodilation despite strong NO scavenging by hemoglobin. The role of N2O3 as a hypothesized stable intermediate for preserving blood nitrite-derived NO will be analyzed using a mass transport model of a microcirculatory arteriole and surrounding tissue.
Second, we propose to develop a cardiac vessel model to determine the role of myocardium myoglobin in regulating NO bioavailability. We hypothesize that cardiac myoglobin plays contrasting roles of scavenging NO during normoxia, but significantly producing NO from endogenous nitrite during ischemia to reduce myocardial infarction size.
Third, a more expansive study of two major tissue nitrite reductases – aldehyde oxidase (AO) and xanthine oxidase (XO) – is proposed to characterize their role in hypoxic NO production. Computational modeling for this study will focus on ischemic and hypoxic conditions in the heart, liver, and kidney microcirculation, where AO and XO nitrite reduction has shown therapeutically beneficial effects. |
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Location:
Bossone Research Center, Room 709, located at 32nd and Market Streets. |
Audience:
Undergraduate StudentsGraduate StudentsFacultyStaff |
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