Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice

Restenosis is due to neointimal hyperplasia, which occurs in the coronary a rtery after percutaneous transluminal coronary angioplasty (PTCA). During r estenosis, an impairment of nitric oxide (NO)-dependent pathways may occur. Concomitant hypercholesterolemia may exacerbate restenosis in patients und ergoing PTCA. Here, we show that a NO-releasing aspirin derivative (NCX-401 6) reduces the degree of restenosis after balloon angioplasty in low-densit y lipoprotein receptor-deficient mice and this effect is associated with re duced vascular smooth muscle cell (VSMC) proliferation and macrophage depos ition at the site of injury. Drugs were administered following both therape utic or preventive protocols. We demonstrate that NCX-4016 is effective bot h in prevention and treatment of restenosis in the presence of hypercholest erolemia. These data indicate that impairment of NO-dependent mechanisms ma y be involved in the development of restenosis in hypercholesterolemic mice . Although experimental models of restenosis may not reflect restenosis in humans in all details, we suggest that a NO-releasing aspirin derivative co uld be an effective drug in reducing restenosis following PTCA, especially in the presence of hypercholesterolemia and/or gastrointestinal damage.