Circulation. 2002;106:599-605
Published online before print July 15, 2002, doi: 10.1161/01.CIR.0000023532.98469.48
Published online before print July 15, 2002, doi: 10.1161/01.CIR.0000023532.98469.48
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(Circulation. 2002;106:599.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits
From the Department of Cardiology, Hadassah-Hebrew University Hospital, Jerusalem, Israel (H.D.D.); the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (I.F., J.G., R.R., I.G., E.M., G.G.); and the Department of Pharmaceutics, University of Kuopio (Finland) (J.M.).
Correspondence to Dr Haim D. Danenberg, Department of Cardiology, Hadassah University Hospital, Jerusalem 91120, Israel (e-mail danen{at}md2.huji.ac.il), or to Dr Gershon Golomb, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Box 12065, Jerusalem 91120, Israel (e-mail golomb@md.huji.ac.il).
Background— Inflammation is critical to vascular repair after mechanical injury. Excessive inflammation enhances neointimal formation and restenosis. We examined whether transient systemic inactivation of macrophages at the time of vascular intervention could attenuate the degree of expected restenosis.
Methods and Results— Liposomal clodronate (LC) inhibited the growth of cultured macrophages but had no effect on endothelial or smooth muscle cells and suppressed neointimal hyperplasia in hypercholesterolemic rabbits and rats after intravenous administration of LC, with no adverse effects. LC treatment reduced the number of blood monocytes and decreased macrophage infiltration in the injured arteries as well as smooth muscle cell proliferation, interleukin-1ß transcription, and production and matrix metalloproteinase-2 activity.
Conclusions— Macrophages play a pivotal role in vascular repair after mechanical arterial injury. Systemic inactivation and depletion of monocytes and macrophages by LC reduce neointimal hyperplasia and restenosis.
Key Words: angioplasty • balloon • restenosis • monocytes • drugs
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