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

Frederick GP Welt

Department of Medicine, Harvard Medical School, Boston, MA, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA, West Roxbury Veteran’s Affairs Medical Center, West Roxbury, MA, USA, welt{at}mit.edu

Colin Tso

Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

Elazer R. Edelman

Department of Medicine, Harvard Medical School, Boston, MA, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

Michael A Kjelsberg

Cardiology Division, Mount Auburn Hospital, Cambridge, MA, USA

John F Paolini

Merck & Co., Inc. West Point, PA, USA

Philip Seifert

Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

Campbell Rogers

Department of Medicine, Harvard Medical School, Boston, MA, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

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 quantifi ed 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 confi ned to early neutrophil infi ltration. 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.

Key Words: chemokines • inflammation • restenosis • stents

Vascular Medicine, Vol. 8, No. 1, 1-7 (2003)
DOI: 10.1191/1358863x03vm462oa


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