The resistance of atherosclerosis to conventional treatments reflects the complex pathogenesis of mature atheroma. The disease is diffuse, but the symptomatic lesions are often localised, and bypassing large stenosing plaques with vein grafts has been the mainstay of palliation. For the past 15 years, however, percutaneous transluminal coronary angioplasty has been used increasingly. In 1990 over 300 000 of these procedures were carried out in the United States1 and about 8500 in Britain.2 This number is still rising, but enthusiasm has been tempered by symptomatic restenosis in about one third of cases.3 Late recoil of the stretched vessel may contribute, but a rapid proliferation of vascular smooth muscle cells within the intima is the striking feature of restenosis, and this fibrocellular intimal hyperplasia has resisted all pharmacological interventions examined so far.3 Attention has turned to less conventional treatments, particularly genetic manipulation of the arterial wall to alter its response to the injury induced by the balloon catheter. To distinguish this local approach from the use of gene therapy to correct inborn errors of metabolism we favour the term molecular therapeutics.

The restenotic lesion after angioplasty can be viewed as part of general …