Leukocyte recruitment and expression of chemokines following different forms of vascular injury

Abstract

Inflammation plays a central role in restenosis following coronary intervention. Recent human and animal data suggest important differences between the inflammatory responses to simple balloon angioplasty compared with stent implantation. To investigate the mechanisms of these differences. New Zealand white rabbits underwent bilateral iliac artery balloon denudation. Half received intravascular stents. Arteries were harvested at three, seven and 14 days for immunohistochemistry, and 4 hours, 8 hours and 14 days for chemokine mRNA analysis. Leukocyte content was quantified utilizing immunohistochemistry (RPN357, monoclonal antibody (mAb) against rabbit neutrophil; RAM-11, mAb against rabbit macrophage). We analyzed the mRNA levels of the chemokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) through semi-quantitative polymerase chain reaction. We demonstrated the spatial pattern of MCP-1 mRNA levels through in situ mRNA hybridization. In balloon-injured arteries, leukocyte recruitment was confined to early neutrophil infiltration. IL-8 and MCP-1 mRNA levels peaked within hours and were undetectable at 14 days. In contrast, in stented arteries, early neutrophil recruitment was followed by prolonged macrophage accumulation. IL-8 and MCP-1 mRNA levels peaked within hours but were still detectable 14 days post injury. Conclusions: In contrast to balloon injury, stent-induced injury results in sustained chemokine expression and leukocyte recruitment. These data may have important implications for antirestenotic strategies.