Role of platelets in restenosis after percutaneous coronary revascularization

Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195-5066, USA. topole@cesmtp.ccf.org

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.

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