Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antibodies, Monoclonal / blood
-
Antibodies, Monoclonal / immunology
-
Antibodies, Monoclonal / pharmacology
-
Blood Vessel Prosthesis Implantation
-
CD18 Antigens / biosynthesis
-
CD18 Antigens / drug effects*
-
Catheterization / adverse effects
-
Disease Progression
-
Graft Occlusion, Vascular / etiology
-
Graft Occlusion, Vascular / pathology
-
Graft Occlusion, Vascular / prevention & control*
-
Hyperplasia / etiology
-
Hyperplasia / pathology
-
Hyperplasia / prevention & control
-
Iliac Artery / pathology
-
Iliac Artery / surgery
-
Immunohistochemistry
-
Leukocytes / drug effects
-
Leukocytes / immunology
-
Leukocytes / metabolism*
-
Macaca fascicularis
-
Macrophages / metabolism
-
Macrophages / pathology
-
Male
-
Monocytes / immunology
-
Monocytes / metabolism
-
Monocytes / pathology
-
Neutrophils / immunology
-
Neutrophils / metabolism
-
Neutrophils / pathology
-
Receptors, CCR2
-
Receptors, Chemokine / antagonists & inhibitors*
-
Receptors, Chemokine / biosynthesis
-
Stents* / adverse effects
-
Tunica Intima / immunology
-
Tunica Intima / pathology
-
Tunica Intima / surgery
-
Vascular Patency / drug effects
-
Vascular Patency / immunology
Substances
-
Antibodies, Monoclonal
-
CD18 Antigens
-
Receptors, CCR2
-
Receptors, Chemokine