Mechanisms of restenosis after angioplasty and approach to therapy (Review).

Angioplasty is a principal treatment for occlusive vascular disease but 30-50% of patients show a restenosis of the vessel. There is no clinical effective therapy for this disease. It has been demonstrated, in animal models, that various drugs such as NO-donor, plasminogen inhibitor tranexamic acid and MMP (matrix metalloproteinases) reduce the rate of restenosis. Other therapeutic approaches are cytotoxic therapy, and strategies to inhibit cell cycle progression. Systemic administration of conventional pharmacologic agents inhibit cell cycle kinases and vascular lesion formation in animal models. As cell cycle progression is accompanied by fluctuations in the concentration of adenosine 3',5-monophospate (cAMP) and in the activity of the cAMP dependent protein kinase (PKA), local administration of cAMP and phospodiesterase-inhibitor drugs (aminophylline or amrinone) markedly inhibit neointima formation. The successful use of local radiation therapy to inhibit neointima formation after vascular injury may reflect a similar combination of cell-cycle arrest and vascular cell apoptosis. The most effective therapy for occlusive vascular disease will likely combine intravascular stenting with an antiproliferative therapy.