Bahnson Edward S M, Havelka George E, Koo Nathaniel C, Jiang Qun, Kibbe Melina R
Division of Vascular Surgery, Northwestern University, Chicago, Illinois; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois.
Division of Vascular Surgery, Northwestern University, Chicago, Illinois; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
J Surg Res. 2016 Oct;205(2):440-445. doi: 10.1016/j.jss.2016.06.074. Epub 2016 Jul 5.
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.
The effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by (3)H-thymidine incorporation in adipocyte-conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague-Dawley rats. Before 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 were assessed via immunofluorescence.
Adipocyte-conditioned media had an antiproliferative effect on 3T3 and AF and a proproliferative 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 wk after surgery compared with the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared with the intact group. Although 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.
These data show that periadventitial adipose tissue plays a role in regulating the arterial injury response and the efficacy of NO treatment in the vasculature.
外膜一氧化氮（NO）递送可抑制内膜增生；然而，外膜脂肪组织对NO抑制内膜增生疗效的影响尚未得到研究。我们研究的目的是评估存在和不存在外膜脂肪组织时NO的作用。我们假设去除外膜脂肪组织会增加内膜形成，并且NO在抑制内膜增生方面会更有效。
通过在脂肪细胞条件培养基或常规培养基中掺入³H-胸腺嘧啶来评估NO对3T3成纤维细胞、外膜成纤维细胞（AF）和血管平滑肌细胞（VSMC）增殖的影响。在雄性Sprague-Dawley大鼠上建立大鼠颈动脉球囊损伤模型。在球囊损伤前，去除外膜脂肪组织（切除模型）或保持完整（完整模型）。治疗组包括损伤组或损伤并在外膜应用PROLI/NO组。通过免疫荧光评估脂联素受体（AR）水平。
脂肪细胞条件培养基在体外对3T3和AF具有抗增殖作用，对VSMC具有促增殖作用。有趣的是，在脂肪细胞条件培养基中，NO在抑制3T3和AF增殖方面效果较差，而在抑制VSMC增殖方面效果更显著。在体内，与完整组相比，切除组在术后2周内膜增生增加。与完整组相比，NO在切除组中能更大程度地减少内膜增生。虽然NO在完整组中抑制或对AR水平无影响，但在切除组的培养基和外膜中，NO增加了AR水平。
这些数据表明，外膜脂肪组织在调节动脉损伤反应和血管系统中NO治疗的疗效方面发挥作用。
