Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice

Eric T. Choi, Emily T. Collins, Leopoldo A. Marine, Maria G. Uberti, Hisashi Uchida, Jeremy E. Leidenfrost, Faisal F. Khan, Kenneth P. Boc, Dana R. Abendschein, William C. Parks

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Objective - Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E (apoE)-deficient (apoE-/-) MMP-9-deficient (MMP-9-/-) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation. Methods and Results - Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE-/- MMP-9 -/- mice had a significant reduction in intimal plaque length and volume compared with apoE-/- MMP-9+/+ mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow-derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE-/- MMP-9+/+ and apoE-/- MMP-9-/- mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development. Conclusions - MMP-9 is derived from resident arterial cells and is required for early atherosclerotic plaque development and cellular accumulation in apoE -/- mice.

Original languageEnglish
Pages (from-to)1020-1025
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number5
DOIs
StatePublished - May 2005

Keywords

  • Atherosclerosis
  • Bone marrow
  • Compartmentalization
  • MMP-9
  • Mouse

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