Published online before print January 31, 2002, doi: 10.1161/hh0402.105956
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© 2002 American Heart Association, Inc.
Integrative Physiology |
Targeting CCR2 or CD18 Inhibits Experimental In-Stent Restenosis in Primates
Inhibitory Potential Depends on Type of Injury and Leukocytes Targeted
From the Department of Medicine, Cardiac Catheterization Laboratory, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass and the Harvard/MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Mass (F.G.P.W., C.R.); the West Roxbury Veteran’s Affairs Medical Center (F.G.P.W.), West Roxbury, Mass; and the Clinical Investigator Training Program, Harvard/MIT Division of Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc (F.G.P.W.), Millennium Pharmaceuticals (C.H., P.R.), Cambridge, Mass, and Primedica Corporation (M.N.), Worcester, Mass.
Correspondence to Frederick G.P. Welt, MD, Harvard-MIT Division of Health Sciences and Technology, MIT, 16-343, Cambridge, MA 02139. E-mail welt{at}mediaone.net
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 ß2-integrin ß-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.
Key Words: stents • leukocytes • primates
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