PHARMACOLOGICAL APPROACHES TO THE PREVENTION OF RESTENOSIS FOLLOWING ANGIOPLASTY - THE SEARCH FOR THE HOLY-GRAIL .1.

Luminal renarrowing after balloon angioplasty still hampers the long term vessel patency in a substantial percentage of patients. Morphologically, the restenotic lesion comprises hyperplasia of intimal tissue, which is mainly characterised by proliferation of smooth muscle cells of the synthetic type with abundant extracellular matrix production, chiefly composed of proteoglycans. Unravelling the underlying pathophysiological process enables more specific intervention in basic interactions and cell responses. Critical events in the development of restenotic tissue are platelet aggregation and thrombus formation, while the release of several mediators promotes proliferation and migration of various cell types. All of these steps give access for a diversity of pharmacological interventions. With this in mind, antithrombotic, antiplatelet, antiproliferative, anti-inflammatory, calcium channel blocking and lipid-lowering drugs have been investigated in the prevention of restenosis. Part II of this article reviews newer approaches, such as antibodies to growth factors, gene transfer and antisense oligonucleotides.