Regulation of smooth muscle cell proliferation and its possible role in preventing restenosis post-angioplasty.

The introduction of balloon angioplasty in 1978 as an alternative treatment for vascular stenosis has created a new clinical problem: restenosis, the renarrowing that occurs after the procedure in certain patients. Restenosis is an important long-term complication, with an incidence of 30-50% within 6 months post-angioplasty. Three mechanisms contribute to vascular restenosis: recoil, thrombus formation and direct trauma. Growth factors which enhance the expression of other growth-regulating proteins, in particular "second messengers", proto-oncogenes and other cell cycle controlling proteins, are released by local thrombi and the injured arterial segment itself, resulting in an excessive inflammatory and myofibroproliferative response which culminates in restenosis. From investigations in animal models it is known that restenosis takes place in several phases: thrombosis, inflammation, cell proliferation and matrix formation. Various factors seem to interact in each particular phase, either as agonists or antagonists; hence the pathway that results in restenosis is complex. The introduction of directional percutaneous atherectomy has made it possible to examine human arterial tissue obtained in vivo, including restenosis material, from a sufficient number of patients in order to complement animal experiments. Not all of the mechanisms which lead to restenosis are known; nevertheless, after more than 15 years' experience of balloon angioplasty, there is an urgent need to develop therapeutic strategies based on currently available information. Selective elimination or alteration of proliferating cells, enhancement of natural growth inhibitors, blocking of signal transduction or inhibition of the gene expression for distinct growth-stimulating proteins all appear to be potentially promising.