4 VIEWS & REVIEWS

Getting closer to the ever elusive amwer to resteoosis

After more than 10 years of clinical experience and research in the field of restenosis after percutaneous transluminal coronary angioplasty (PTCA), there have been no major breakthroughs in pharmacological interventions. And so, enormous effort continues to be invested in this area. Whether such endeavour is only searching for the 'Holy Grail', or whether there is a feasible drug treatment that works on the process of restenosis, without serious adverse effects, remains uncertain.

Despite these reservations, progress is being made. The future success of restenosis prevention may lie in molecular biology, as outlined by Jean-Paul Herrman and colleagues, from Erasmus University, Rotterdam, Netherlands.

New approaches Several studies have indicated that growth

factors playa significant role in the response of smooth muscle cells to vessel wall injury, and some success has been seen with antibodies to these factors in animal models. As inositol diphosphate is involved in the process by which growth factors stimulate cell proliferation, agents which inhibit inositol-phospholipid metabolism may be useful for preventing restenosis after PTCA.

First steps are also being taken in exploring the possibilities of genetic manipulation, and it has been demonstrated that human vascular smooth muscle cells can be drastically affected by such an approach.

Sense-antisense approaches, whereby oligonucleotides are used to block messenger RNA action, are also being investigated. Using this technique in rat carotid arteries, researchers showed that smooth muscle cell accumulation was minimised compared with controls.

Alteration of proto-oncogene expression is a very attractive concept, and developments in this field might result in complete interruption of the hyperplastic response of intimal tissue, at the level of the ultimate common pathway, concluded Herrman and colleagues. Hemnan J.pR. Hennans WRM. \bs J. Serruys pw. PhannacologicaJ approaches to the prevention of restenosis foUowing angioplasty. The search for the Holy Grail? (Part m. Drugs 46: 249-262. Aug 1993 1m2"'1J

14 Aug 1993 INPHARMAe ISSN 0156-270319310814-0041$1.00"' Adl8lnternat1onal Ltd