Dual role of matrix metalloproteinases-2 in thoracic aortic aneurysm

  • Author / Creator
    Lee, Ji Won
  • With matrix metalloproteinases-2 (MMP2) deficiency, we observed thoracic aortic aneurysm in 70% of MMP2-/- mice but no abdominal aortic aneurysm following four weeks of angiotensin II (Ang II) infusion. We found markedly suppressed recoil properties in the thoracic aorta of MMP2-/-- Ang II mice. mRNA and protein levels of elastin, but not collagen, were significantly reduced in the thoracic aorta of MMP2-/--Ang II compared to WT-Ang II mice. This reduction in elastin levels was due to significantly reduced TGFβ-Smad signaling pathway that mediates synthesis of extracellular components. Thus, the adverse remodeling in the thoracic aorta of MMP2-deficient mice was associated with decreased synthesis of extracellular matrix proteins without concomitant upregulation of proteolytic activities. These findings suggest a protective role of MMP2 in the development and progression of aortic aneurysm, and as such inhibition of MMP2 may exacerbate vascular remodeling and lead to development of thoracic aortic aneurysm.

  • 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
    • Department of Physiology
  • Supervisor / co-supervisor and their department(s)
    • Kassiri, Zamaneh (Physiology)
  • Examining committee members and their departments
    • McMurtry, Sean (Medicine)
    • Davidge, Sandra (Obstetrics & Gynaecology)
    • Fernandez-Patron, Carlos (Biochemistry)