Leukocyte recruitment and expression of chemokines following different forms of vascular injury.
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.
Welt
Frederick G P
FG
Department of Medicine, Harvard Medical School, Boston, MA, USA. welt@mit.edu
Tso
Colin
C
Edelman
Elazer R
ER
Kjelsberg
Michael A
MA
Paolini
John F
JF
Seifert
Philip
P
Rogers
Campbell
C
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects*; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology / Q000293:injuries* / Q000601:surgery*; D015870:Gene Expression / Q000235:genetics* / Q000276:immunology*; D007083:Iliac Artery / Q000276:immunology / Q000293:injuries / Q000601:surgery; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D007958:Leukocyte Count; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D011817:Rabbits; D015607:Stents / Q000009:adverse effects*; D013997:Time Factors
D018932:Chemokine CCL2; D016209:Interleukin-8; D012333:RNA, Messenger