Paszkowiak Jacek J, Maloney Stephen P, Kudo Fabio A, Muto Akihito, Teso Desarom, Rutland Reuben C, Westvik Tormod S, Pimiento Jose M, Tellides George, Sessa William C, Dardik Alan
Department of Surgery, Yale University School of Medicine, New Haven, CT 06519, United States.
Vascul Pharmacol. 2007 Apr;46(4):293-301. doi: 10.1016/j.vph.2006.11.003. Epub 2006 Nov 18.
Both neointimal hyperplasia and inward remodeling contribute to restenosis and lumen loss. Nogo-B has been recently described as an inhibitor of vascular injury and neointimal hyperplasia. To determine whether Nogo-B expression may be a mediator of inward remodeling, we examine the localization of expression of Nogo-B in an in vivo model that examines both neointimal hyperplasia and inward remodeling. The rabbit carotid artery was subjected to balloon injury, outflow branch ligation to reduce flow, or both balloon injury and reduction in flow. In balloon injury-induced neointimal hyperplasia Nogo-B expression was reduced in the intima and media but stimulated in the adventitia. In low flow-induced inward remodeling medial Nogo-B expression was not reduced and adventitial Nogo-B expression was not stimulated. Low flow significantly augmented balloon injury-induced neointimal hyperplasia and was accompanied by reduced intimal and medial Nogo-B expression, and increased adventitial Nogo-B expression in both smooth muscle cells and macrophages. Low flow-induced inward remodeling is not associated with changes in medial Nogo-B expression and is distinct from injury-induced neointimal hyperplasia. Pharmacological strategies to inhibit neointimal hyperplasia and restenosis using normal flow models may only partially account for lumen loss and therefore may not accurately predict responses in patients with extensive outflow disease.
新生内膜增生和血管内向重塑均会导致再狭窄和管腔狭窄。Nogo-B最近被描述为血管损伤和新生内膜增生的抑制剂。为了确定Nogo-B的表达是否可能是血管内向重塑的介质，我们在一个同时研究新生内膜增生和血管内向重塑的体内模型中检测了Nogo-B的表达定位。对兔颈动脉进行球囊损伤、结扎流出分支以减少血流，或同时进行球囊损伤和血流减少。在球囊损伤诱导的新生内膜增生中，内膜和中膜中的Nogo-B表达减少，但外膜中的表达受到刺激。在低血流诱导的血管内向重塑中，中膜Nogo-B表达未减少，外膜Nogo-B表达未受到刺激。低血流显著增强了球囊损伤诱导的新生内膜增生，并伴有内膜和中膜Nogo-B表达减少，以及外膜Nogo-B在平滑肌细胞和巨噬细胞中的表达增加。低血流诱导的血管内向重塑与中膜Nogo-B表达的变化无关，且与损伤诱导的新生内膜增生不同。使用正常血流模型抑制新生内膜增生和再狭窄的药理学策略可能只能部分解释管腔狭窄，因此可能无法准确预测患有广泛流出道疾病患者的反应。
