Napoli C, Cirino G, Del Soldato P, Sorrentino R, Sica V, Condorelli M, Pinto A, Ignarro L J
Department of Medicine, Federico II University of Naples, 80131 Naples, Italy.
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2860-4. doi: 10.1073/pnas.041602898.
Restenosis is due to neointimal hyperplasia, which occurs in the coronary artery after percutaneous transluminal coronary angioplasty (PTCA). During restenosis, an impairment of nitric oxide (NO)-dependent pathways may occur. Concomitant hypercholesterolemia may exacerbate restenosis in patients undergoing PTCA. Here, we show that a NO-releasing aspirin derivative (NCX-4016) reduces the degree of restenosis after balloon angioplasty in low-density lipoprotein receptor-deficient mice and this effect is associated with reduced vascular smooth muscle cell (VSMC) proliferation and macrophage deposition at the site of injury. Drugs were administered following both therapeutic or preventive protocols. We demonstrate that NCX-4016 is effective both in prevention and treatment of restenosis in the presence of hypercholesterolemia. These data indicate that impairment of NO-dependent mechanisms may 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 could be an effective drug in reducing restenosis following PTCA, especially in the presence of hypercholesterolemia and/or gastrointestinal damage.
再狭窄是由新生内膜增生引起的，这发生在经皮腔内冠状动脉成形术（PTCA）后的冠状动脉中。在再狭窄过程中，可能会出现一氧化氮（NO）依赖途径的损害。伴有高胆固醇血症可能会加重接受PTCA患者的再狭窄。在此，我们表明一种释放NO的阿司匹林衍生物（NCX - 4016）可降低低密度脂蛋白受体缺陷小鼠球囊血管成形术后的再狭窄程度，且这种作用与损伤部位血管平滑肌细胞（VSMC）增殖和巨噬细胞沉积减少有关。药物按照治疗或预防方案给药。我们证明在存在高胆固醇血症的情况下，NCX - 4016在预防和治疗再狭窄方面均有效。这些数据表明NO依赖机制的损害可能参与了高胆固醇血症小鼠再狭窄的发生。尽管再狭窄的实验模型可能无法在所有细节上反映人类的再狭窄情况，但我们认为一种释放NO的阿司匹林衍生物可能是降低PTCA后再狭窄的有效药物，尤其是在存在高胆固醇血症和/或胃肠道损伤的情况下。
