Abstract

Chronic hypoxia complicates many pregnancies and can result in postnatal pathologies that include compromised fetal cardiovascular structure and function. Mechanisms involved remain unclear. Because hypoxia increases production of VEGF, known to modulate smooth muscle (SM) phenotype, this thesis explored the hypothesis that VEGF contributes to hypoxic fetal vascular remodeling through direct effects on SM cells and indirectly through perivascular nerves. Using a chronic hypoxia sheep model, this work demonstrated that: 1) hypoxia potently upregulates VEGF receptor expression but not endogenous VEGF level in fetal ovine carotid arteries; 2) both chronic hypoxia and VEGF exert similar effects on smooth muscle contractile proteins; 3) both chronic hypoxia and VEGF exert similar effects on contractile protein colocalizations; and lastly, sympathetic autonomic nerves contribute to hypoxic reorganization of structure and function of vascular contractile proteins. Together, these findings advance understanding of how hypoxia precipitates fetal vascular remodeling and offer an essential first step toward finding new treatments for infants that survive in-utero hypoxia.

LLU Discipline

Physiology

Department

Basic Sciences

School

School of Medicine

First Advisor

Pearce, William J.

Second Advisor

Damon, Deborah

Third Advisor

Ducsay, Charles

Fourth Advisor

Mata-Greenwood, Eugenia

Fifth Advisor

Zhang, Lubo

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

January 2013

Date (Title Page)

6-1-2013

Language

English

Library of Congress/MESH Subject Headings

Fetal hypoxia; Fetal development; Endothelium, vascular; Cardiovascular system - physiopathology; Fetal heart - physiopathology; Hypoxia-Ischemia, Brain - physiopathology

Subject - Local

Ovine cranial arteries, Sympathetic perivascular nerves, VEGF, Hypoxia, Vascular Endothelial Growth factor, Chronic hypoxia, Hypoxic fetal vascular remodeling

Type

Dissertation

Page Count

174 p.

Digital Format

Application/PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses & Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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