Published online before print May 20, 2002, doi: 10.1161/01.CIR.0000016825.17448.11
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(Circulation. 2002;105:2686.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Expansive Arterial Remodeling Is Associated With Increased Neointimal Macrophage Foam Cell Content
The Murine Model of Macrophage-Rich Carotid Artery Lesions
From the Division of Cardiology, Emory University School of Medicine (E.I., D.G., S.N., S.L., J.K., Z.G.), and the Department of Biomedical Engineering (C.J., R.M., Z.G.), Georgia Institute of Technology, Atlanta, Ga.
Correspondence to Zorina S. Galis, PhD, Departments of Medicine and Biomedical Engineering, Emory University School of Medicine, 1639 Pierce Dr, WMB 319, Atlanta, GA 30322. E-mail zgalis{at}emory.edu
Background— Recent observations associate plaque instability with expansive arterial remodeling, suggesting a common driving mechanism.
Methods and Results— To demonstrate that macrophages, a characteristic of vulnerable plaques, also assist in expansive remodeling, we compared carotid artery remodeling due to formation of experimental macrophage-rich and macrophage-poor lesions in the flow cessation model in hypercholesterolemic apolipoprotein E knockout (ApoE KO) and wild type (WT) mice. After ligation, macrophages started to rapidly accumulate in ApoE KO but not in WT carotid artery lesions. Macrophage-rich ApoE KO intimal lesions grew fast, typically occluding within 14 days, despite a tripling of the vessel area. Outward remodeling of macrophage-rich ApoE KO arteries positively correlated with macrophage area (r2=0.600, P<0.001). To investigate potential mechanisms of macrophage-enabled expansive remodeling, we compared levels of matrix metalloproteinases in homogenates of macrophage-rich and macrophage-poor carotid arteries. Gelatinolytic activity of macrophage-rich lesions increased faster and reached maximal levels several fold higher than in the macrophage-poor WT lesions.
Conclusions— Our results suggest that macrophages facilitate expansive arterial remodeling through increased matrix degradation by matrix metalloproteinases. This initially favorable remodeling action may eventually increase the vulnerability of macrophage-rich atherosclerotic plaques.
Key Words: atherosclerosis • hypercholesterolemia • metalloproteinases • leukocytes • remodeling
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