Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits

作者：Haim D Danenberg, Ilia Fishbein, Jianchuan Gao, Jukka Mönkkönen, Reuven Reich, Irith Gati, Evgeny Moerman, Gershon Golomb · 发表于：Circulation · 年份：2002 · DOI：10.1161/01.cir.0000023532.98469.48 · 被引用次数：253 · 研究领域：Bone health and treatments、Caveolin-1 and cellular processes、Infectious Aortic and Vascular Conditions

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-1beta 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.