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Thromb Haemost 2004; 91(06): 1186-1193
DOI: 10.1160/TH03-11-0701
Wound Healing and Inflammation/Infection
Schattauer GmbH

Prevention of in-stent restenosis via reduction of thrombo-inflammatory reactions with recombinant P-selectin glycoprotein ligand-1

Jean-François Tanguay
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
,
Pascale Geoffroy
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
,
Martin G. Sirois
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
,
Danielle Libersan
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
,
Anjali Kumar
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
2   Wyeth Research, Cambridge Massachusetts, USA
,
Robert G. Schaub
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
2   Wyeth Research, Cambridge Massachusetts, USA
,
Yahye Merhi
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
1   Research Center, Montreal Heart Institute, Montreal, Quebec, Canada, University of Montreal, Montreal, Quebec, Canada
› Author AffiliationsFinancial support: This work was supported by the Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada
Further Information

Publication History

Received 18 November 2003

Accepted after revision 01 March 2004

Publication Date:
02 December 2017 (online)

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Summary

The binding of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) to platelet P-selectin is central to post-angioplasty restenosis. Although intracoronary stents limit the mechanical component of restenosis, they cause marked thrombo-inflammation and neointimal proliferation leading to greater late luminal loss. We sought to demonstrate that P-selectin antagonism, using recombinant PSGL-1 (rPSGL-Ig), is effective in reducing platelet-leukocyte reactions and in-stent restenosis in doubleinjured porcine coronary arteries. Two weeks after initial injury by angioplasty to the coronary arteries, stents were implanted at the injury-induced lesion site, 15 min after an IV bolus administration of a vehicle or rPSGL-Ig (1 mg/kg). Four weeks later, adhesion of 51Cr-platelets and 111In-neutrophils and histomorphometric analyses were performed. In-stent residual lumen was almost 3 fold larger in rPSGL-Ig-treated arteries (3.1 ± 0.4 mm2) as compared to control (1.1 ± 0.2 mm2), which correspond to 64% vascular stenosis in control with no change in rPSGL-Ig animals. For a similar injury score, in-stent neointima was significantly reduced by 30 to 40% in the rPSGL-Ig group and quantitative coronary angiography showed a significant 35% reduction in late lumen loss. These effects of rPSGL-Ig were associated with a respective 70% and 53% reduction in platelet and neutrophil adhesion. In conclusion, pretreatment with rPSGL-Ig reduces thrombo-inflammatory responses, neointimal proliferation, and in-stent restenosis. P-selectin antagonism offers a promising therapy to improve clinical outcomes of coronary stenting.

Keywords

Restenosis - stents - leukocytes - platelets - P-selectin - PSGL-1
 

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