Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates - Inhibitory potential depends on type of injury and leukocytes targeted

被引:111
作者
Horvath, C
Welt, FGP [1 ]
Nedelman, M
Rao, P
Rogers, C
机构
[1] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiac Catheterizat Lab,Cardiovasc Div, Boston, MA 02115 USA
[3] W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA
[4] Pfizer Inc, Millenium Pharmaceut, Clin Investigator Training Program, Cambridge, MA USA
[5] Primedica Corp, Worcester, MA USA
关键词
stents; leukocytes; primates;
D O I
10.1161/hh0402.105956
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
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 beta(2)-integrin beta-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.
引用
收藏
页码:488 / 494
页数:7
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