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Role of platelets in restenosis after percutaneous coronary revascularization
H Le Breton1, E F Plow, E J Topol
1Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195-5066, USA. topole@cesmtp.ccf.org
Insights
Platelets play a key role in restenosis after coronary angioplasty. The drug abciximab may reduce restenosis by targeting the alpha v beta 3 integrin receptor, suggesting a new mechanism of action.
Area of Science:
- Cardiovascular Biology
- Hematology
- Interventional Cardiology
Background:
- Platelets are activated following vascular injury, releasing growth factors and expressing adhesion molecules.
- Platelets are implicated as mediators in the vascular injury response, potentially contributing to restenosis.
- Experimental models suggest blocking platelet receptors may reduce neointimal hyperplasia, but clinical trials have yielded mixed results.
Purpose of the Study:
- To investigate the role of platelets in restenosis after percutaneous coronary intervention.
- To explore the mechanism by which abciximab reduces clinical restenosis.
- To examine the potential involvement of the alpha v beta 3 vitronectin receptor in abciximab's effect.
Main Methods:
- Review of experimental models and clinical trial data on platelet inhibition in restenosis.
- Analysis of abciximab's cross-reactivity with the alpha v beta 3 integrin.
- Comparison of abciximab's mechanism with other glycoprotein IIb/IIIa inhibitors.
Main Results:
- Platelet activation, adhesion, and aggregation are significant after vascular injury.
- Abciximab, a glycoprotein IIb/IIIa inhibitor, demonstrated a 26% reduction in clinical restenosis.
- Abciximab cross-reacts with the alpha v beta 3 vitronectin receptor, which is involved in smooth muscle cell migration.
Conclusions:
- Platelets are pivotal in the vascular injury response and restenosis.
- Abciximab's benefit in reducing restenosis may be mediated through the alpha v beta 3 integrin.
- Further research is needed to fully elucidate the complex role of platelets in restenosis.
Abstract:
The role of platelets in the process of restenosis after percutaneous coronary intervention is not fully understood. After vascular injury there is extensive platelet activation, adhesion, aggregation and secretion. Through the liberation of growth factors, such as platelet-derived growth factor, and surface expression of cell adhesion molecules, such as the glycoprotein IIb/IIIa integrin, platelets appear to be a pivotal mediator of the vascular injury response. Experimental models have demonstrated that profound, prolonged thrombocytopenia, or blockade of the IIb/IIIa receptor, may reduce neointimal hyperplasia after arterial balloon injury. However, multiple clinical trials testing conventional or new platelet agents have not yielded any salutary effects. The recent finding that abciximab, a monoclonal antibody fragment directed against IIb/IIIa, reduced clinical restenosis after coronary angioplasty by 26% in patients raises questions about the mechanism of benefit. The alpha v beta 3 vitronectin receptor is responsible for binding endothelial cells to platelets, and it also has a key role in modulating smooth muscle cell migration. It is possible that the antibody fragment exerts its effect on restenosis by means of alpha v beta 3, because abciximab fully cross-reacts to this integrin owing to the shared beta 3 subunit. To date, the other platelet glycoprotein IIb/IIIa inhibitors, including Integrelin, Tirofiban, Lamifiban and Xemilofiban, are specific in binding to this particular integrin. Considerable further study is necessary to unravel the effects of platelets on the restenosis process.