Role of Platelets in Restenosis After Percutaneous Coronary Revascularization

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/III integrin, platelets appear to be pivotal mediator of the vascular injury response. Experimental models have demonstrated that profound, prolonged thrombocytopenia, or blockade of the IIb/III receptor, may reduce neointimal hyperplasi 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, 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 αvβ3 vitronectin receptor is responsible for binding endothelial cells to platelets, and it also has key role in modulating smooth muscle cell migration. It is possible that the antibody fragment exerts its effect on restenosis by means of αvβ3, because abciximab fully cross-reacts to this integrin owing to the shared β3 subunit. To date, the other platelet glycoprotein IIb/III 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.