RAT ARTERIAL-WALL RETAINS MYOINTIMAL HYPERPLASTIC POTENTIAL LONG AFTER ARTERIAL INJURY

Background Many novel molecular and pharmacological modalities have be en proposed for the treatment of accelerated vascular diseases. Yet th e fundamental question remains of whether the vessel wall can be treat ed once only or whether single-dose therapy simply delays the inevitab le processes that lead to intimal hyperplasia. Since platelet adhesion and aggregation are critical events in vascular healing, we sought to determine whether the injured blood vessel would retain its myointima l potential after reversal of even prolonged periods of thrombocytopen ia. Methods and Results A novel nonimmune method sustained thrombocyto penia and suppressed postinjury neointimal hyperplasia by 88%. Infusio n of fresh platelets, even 14 days after initial denuding injury, rest ored the full neointimal hyperplastic potential. Platelet depletion pr esumably removed factors chemotactic for vascular smooth muscle cells but had no effect on the overexpression of the platelet-derived growth factor receptor-beta (PDGFR-beta) subunit after vascular injury. In n ative vessels, 26.5+/-2.5% of medial smooth muscle cells expressed PDG FR-beta. In all animals, medial PDGFR-beta expression doubled 2 weeks after endothelial denudation and was evident in up to 74.5+/-2.5% of t he cells forming the neointima. Conclusions Thus, though the hyperplas tic potential of the injured blood vessel can be delayed with removal of growth stimuli, it is not lost forever, and if the media is not mad e quiescent, neointimal hyperplasia is simply delayed rather than prev ented. These results may have a profound effect on our understanding a nd treatment of accelerated proliferative vascular diseases.