Targeting CCR2 or CD18 Inhibits Experimental In-Stent Restenosis in PrimatesInhibitory Potential Depends on Type of Injury and Leukocytes Targeted
作者:
Christopher Horvath,
Frederick Welt,
Mark Nedelman,
Patricia Rao,
Campbell Rogers,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 90,
issue 4
页码: 488-494
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: stents;leukocytes;primates
数据来源: OVID
摘要:
A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and spatial distribution of different leukocytes after balloon and stent-induced injury in primate iliac arteries. Based on these data, we targeted neutrophil and monocyte recruitment selectively after angioplasty or stent implantation and demonstrated that monocyte-specific blockade achieved via blockade of the MCP-1 receptor CCR2, was effective at reducing neointimal hyperplasia after stenting. In contrast, combined neutrophil and monocyte blockade achieved by targeting the leukocyte &bgr;2-integrin &bgr;-subunit CD18 was required to reduce neointimal hyperplasia after balloon injury. Distinct patterns of leukocyte infiltration in balloon versus stent-injured arteries predict distinct mechanisms for antiinflammatory strategies targeting neutrophils or monocytes in primates and may assist design of effective clinical strategies for optimizing vascular interventions.
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