Cytomegalovirus and Vascular Function During Pregnancy

• Author / Creator

  Gombos, Randi B

• 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.

• Subjects / Keywords

  • Mesenteric artery
  • Uterine artery
  • Vascular responses
  • Vasodilation
  • Pregnancy
  • Sphingosine 1-phosphate
  • Mouse
  • Methacholine
  • Cytomegalovirus
  • Vasoconstriction

• Graduation date

  Spring 2012

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3SM7V

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.