HEPARIN DOES NOT INHIBIT ONCOGENE INDUCTION IN RABBIT AORTA FOLLOWINGBALLOON DENUDATION

Objective: Smooth musle cell proliferation and migration are the predo minant responses to intimal and medial injury after percutaneous trans luminal coronary angioplasty. The in vivo inhibitory effect of heparin on these responses is well documented. To test the hypothesis that th e antiproliferative effect of heparin in vivo may be related to an inh ibition of proto-oncogene expression, the effects of pretreatment with heparin on the expression of the c-myc, c-fos and c-jun proto-oncogen es were examined in a rabbit model of balloon denudation. Methods: Ani mals were randomised 5 h before balloon denudation to receive a subcut aneous injection of unfractionated heparin (7500 IU.kg-1, n=7) or sali ne (n=6). Total RNA extracted from the aorta 1 h after balloon denudat ion was analysed by northern blot technique. A histological study was also performed in saline treated (n=4) and heparin treated (n=4) anima ls 28 d after balloon denudation. Results: The histological study show ed that the degree of neointimal thickening was significantly less in heparin treated animals. However, the level of expression of the proto -oncogenes we studied was similar in both groups. Conclusions: Heparin inhibits neointimal thickening after balloon denudation. This inhibit ion is not associated with an overall decrease in the level of express ion of the c-myc, c-fos, or c-jun proto-oncogenes in the arterial wall , suggesting that the antiproliferative effect of heparin may be due t o an effect on other events in the cell cycle.