on March 3, 2005
Published online before print March 3, 2005, doi: 10.1161/01.ATV.0000161275.82687.f6
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Submitted on September 19, 2003
Accepted on February 16, 2005
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 *;
From the Departments of Surgery (E.T. Choi, E.T. Collins, L.A.M., M.G.U., H.U., J.E.L., K.P.B.) and Internal Medicine (M.F.K., D.R.A.), Washington University School of Medicine, St. Louis, Mo; and the Department of Medicine (W.C.P.), University of Washington, Seattle.
* To whom correspondence should be addressed. E-mail: choie{at}msnotes.wustl.edu.
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.
Key words: atherosclerosis • MMP-9 • bone marrow • mouse • compartmentalization
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