A paradigm for restenosis after angioplasty: clues for the development of new preventive therapies

Restenosis after intravascular intervention is one of the most important unsolved clinical and economic problems in the management of cardiovascular disease. Although neither its pathogenesis nor its prevention are yet defined, the early and late histologic appearance of the angioplasty state are known. Immediately after angioplasty, the atheroma has fissures, and the normal segment of the vessel circumference is stretched. There is substantial evidence of intimal injury. When restenosis develops at 1-4 months the histologic appearance of the restenotic lesion is intimal hyperplasia. Given this endpoint, we may theorize that the proximate cause of this response is denuding and stretching vascular injury. Since the healing response to tissue injury has been studied extensively, we can hypothesize the major milestones in the temporal sequence of restenosis are platelet aggregation, inflammatory cell infiltration, release of growth factors, medial smooth muscle cell modulation and proliferation, proteoglycan synthesis and extracellular matrix remodeling. At each of these steps, there are potential inhibitors. The resolution of the problem of restenosis may require both removal of atheroma mass and appropriate timing and effective delivery of inhibitors of intimal hyperplasia to the injury site in adequate concentration. Biomedical Reviews 1992; 1: 13-24.