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Cytomegalovirus and Vascular Function During Pregnancy Open Access


Other title
Sphingosine 1-phosphate
Uterine artery
Mesenteric artery
Vascular responses
Type of item
Degree grantor
University of Alberta
Author or creator
Gombos, Randi B
Supervisor and department
Mitchell, Bryan F (Physiology; Obstetrics and Gynecology)
Hemmings, Denise G (Obstetrics and Gynecology; Medical Microbiology and Immunology)
Examining committee member and department
Jain, Venu (Obstetrics and Gynecology)
Lee, Bonita (Pediatrics; Medical Microbiology and Immunology)
Davidge, Sandra T (Physiology; Obstetrics and Gynecology)
Pyne, Susan (Pharmacy and Biomedical Sciences)
Department of Physiology

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Human cytomegalovirus (HCMV) is implicated in several vascular diseases through endothelial dysfunction. Most of the research on CMV has focused on either congenital CMV infections or CMV disease in immunocompromised hosts; however, CMV has also been associated with vascular diseases in immunocompetent individuals, including atherosclerosis and the pregnancy-specific disorder preeclampsia. A direct connection between CMV and vascular dysfunction remains unknown. Therefore, in the presence or absence of an active CMV infection, I chose to study the systemic (mesenteric) and uterine vascular responses in intact, isolated arteries from non-pregnant (NP) and late pregnant (LP) mice. Furthermore, I investigated if a maternal CMV infection leads to poor fetal outcomes, independent of a congenital infection. Viral transmission to the fetus does not occur in the mouse, making it a useful model for studying maternal CMV infections. Sensitivity to the α1-adrenergic receptor agonist, phenylephrine (PE), was decreased, sphingosine 1-phosphate (S1P)-induced vasodilation was decreased, and cholinergic (methacholine (ME)) vasodilation was increased in mesenteric arteries from CMV-infected NP and LP mice. Nitric oxide (NO) and prostanoid mediation of endothelium-dependent vasodilation were also increased in these arteries. In uterine arteries from CMV-infected NP mice, ME-induced vasodilation was increased with smooth muscle sensitivity to NO, similar to mesenteric arteries from CMV-infected NP mice. In addition, early interactions of CMV with endothelial cells increased sensitivity to ME in the absence of a fully systemic CMV infection. In contrast, PE-induced vasoconstriction was increased and sensitivity to ME and ME-induced vasodilation were decreased in uterine arteries from CMV-infected LP mice. NO and prostanoid mediation were unaltered in the presence of a CMV infection; hence, decreased EDHF likely contributed to the reduced cholinergic sensitivity and vasodilation. Vascular dysfunction observed in these arteries was dependent on a systemic CMV infection. Finally, the pregnancy outcome was largely affected by genotypic susceptibility to CMV. C57Bl/6J mice were able to compensate for a CMV infection (normal fetal growth) whereas CMV-infected Balb/cJ mice (more susceptible) were infertile. Together, my findings provide evidence that an active CMV infection is a risk factor for vascular and fetal complications during pregnancy and potentially other cardiovascular diseases in the general population.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Gombos, RB, Wolan, V, McDonald, K, Hemmings, DG (2009) Impaired vascular function in mice with an active cytomegalovirus infection. Am J Physiol Heart Circ Physiol 296(4): H937-945.Gombos, RB, Hemmings, DG (2010) Differential effects on nitric oxide-mediated vasodilation in mesenteric and uterine arteries from cytomegalovirus-infected mice. Am J Physiol Heart Circ Physiol 299(4): H1124-1134.

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