The Role of Matrix Metalloproteinase-2 in the Pathophysiology of a Reduced Utero-Placental Perfusion Pressure Model of Preeclampsia

  • Author / Creator
    Abdalvand, Ali
  • Preeclampsia is a leading cause of maternal and fetal morbidity/mortality and induced preterm birth. Endothelin-1 (ET-1) is a potent vasoactive agent, shown to be involved in the vascular endothelial dysfunction of preeclampsia. Big endothelin (bigET) is cleaved to ET-1 by several enzymes including matrix metalloproteinase-2 (MMP-2). I hypothesized that increased levels and/or activity of MMP-2 may lead to enhanced production of ET-1 and thus increase vasoconstriction in preeclampsia. I used the reduced utero-placental perfusion pressure (RUPP) model of preeclampsia and studied vascular function using mesenteric arteries from Sham and RUPP to test my hypothesis. I showed that: 1) vascular contractility in response to bigET was greater in RUPP, 2) the contribution of MMP-2 to bigET to ET-1 cleavage was greater in RUPP, 3) nitric oxide can modulate the function of MMP-2 and several other bigET cleaving enzymes. These novel findings can provide avenues for new therapeutic approaches to preeclampsia.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • 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.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Medical Sciences- Obstetrics and Gynecology
  • Supervisor / co-supervisor and their department(s)
    • Davidge, Sandra (Obstetrics and Gynecology / Physiology)
  • Examining committee members and their departments
    • Chari, Radha (Obstetrics and Gynecology)
    • Mitchel, Bryan(Peter) (Obstetrics and Gynecology / Physiology)
    • Kassiri, Zam (Physiology)