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.
School of Medicine
Pearce, William J.
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
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
Loma Linda University Libraries
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.
Adeoye, Olayemi Olufikayo, "VEGF and Sympathetic Perivascular Nerves Contribute to Hypoxic Remodeling of Ovine Cranial Arteries" (2013). Loma Linda University Electronic Theses, Dissertations & Projects. 110.
Loma Linda University Electronic Theses & Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives