Periadventitial adipose tissue modulates the effect of PROLI/NO on neointimal hyperplasia

Abstract

Background Periadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia, however the effect of periadventitial adipose tissue on the efficacy of NO at inhibiting neointimal hyperplasia has not been studied. The aim of our study was to assess the effect of NO in the presence and absence of periadventitial adipose tissue. We hypothesized that removal of periadventitial adipose tissue will increase neointimal formation and that NO will be more effective at inhibiting neointimal hyperplasia. Methods The effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by 3H-thymidine incorporation in adipocyte-conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague Dawley rats. Prior to balloon injury, periadventitial adipose tissue was removed (excised model) or remained intact (intact model). Treatment groups included injury or injury with periadventitial application of PROLI/NO. Adiponectin receptor (AR) levels was assessed via immunofluorescence. Results Adipocyte-conditioned media had an anti-proliferative effect on 3T3 and AF, and a pro-proliferative effect on VSMC in vitro. Interestingly, NO was less effective at inhibiting 3T3 and AF proliferation and more effective at inhibiting VSMC proliferation in adipocyte-conditioned media. In vivo, the excised group showed increased neointimal hyperplasia 2 weeks after surgery compared to the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared to the intact group. While NO inhibited or had no impact on AR levels in the intact group, NO increased AR levels in media and adventitia of the excised group. Conclusions These data show that periadventitial adipose tissue plays a role in regulating the arterial injury response as well as the efficacy of NO treatment in the vasculature.