Faries P L, Marin M L, Veith F J, Ramirez J A, Suggs W D, Parsons R E, Sanchez L A, Lyon R T
Department of Surgery, Montefiore Medical Center, University Hospital for the Albert Einstein College of Medicine, New York, N.Y. 10467, USA.
J Vasc Surg. 1996 Sep;24(3):463-71. doi: 10.1016/s0741-5214(96)70203-3.
Vein graft stenosis caused by intimal hyperplasia (IH) accounts for 30% to 50% of late bypass graft failures; however, the biochemical mediators of vein graft IH have been poorly defined. We attempted to evaluate the spatial and temporal distribution of five principal cytokines (interleukin-1 beta [IL-1 beta], platelet-derived growth factor-AA [PDGF-AA], basic fibroblast growth factor [bFGF], interferon gamma [INF gamma], and tumor necrosis factor alpha [TNF-alpha]) during the development of IH in a rat vein graft model.
Rat epigastric vein interposition grafts in the femoral artery were harvested at 6 hours, 2 days, 1 week, 2 weeks, and 4 weeks after the grafting procedure and studied with immunohistochemical and standard histologic techniques. The cytokine expression in the endothelium and media/neointima was quantified as the percentage of immunopositive cells per high-power field.
Maximal hyperplasia occurred 2 weeks after the grafting procedure. Peak expression of IL-1 beta and bFGF occurred by 2 days. PDGF-AA expression paralleled the development of IH, peaking at 2 weeks and then declining. TNF-alpha expression increased at 1 week and remained elevated. INF gamma was seen only in control grafts.
The coordinated early release of IL-1 beta and bFGF and the down-regulation of INF gamma seem to trigger an inflammatory response, thereby initiating IH. The process then is propagated by the release of PDGF-AA and TNF-alpha, with concomitant smooth muscle cell proliferation and production of extracellular matrix. It is likely that this complex milieu of local paracrine signaling is required to generate the hyperplastic response seen in failing vein grafts.
内膜增生（IH）导致的静脉移植物狭窄占晚期旁路移植物失败的30%至50%；然而，静脉移植物IH的生化介质尚未明确。我们试图在大鼠静脉移植物模型中评估IH发展过程中五种主要细胞因子（白细胞介素-1β[IL-1β]、血小板衍生生长因子-AA[PDGF-AA]、碱性成纤维细胞生长因子[bFGF]、干扰素γ[INFγ]和肿瘤坏死因子α[TNF-α]）的时空分布。
在移植手术后6小时、2天、1周、2周和4周，采集大鼠股动脉中的腹壁静脉间置移植物，并用免疫组织化学和标准组织学技术进行研究。将内皮和中膜/新生内膜中的细胞因子表达定量为每高倍视野免疫阳性细胞的百分比。
移植手术后2周出现最大增生。IL-1β和bFGF的峰值表达在2天时出现。PDGF-AA的表达与IH的发展平行，在2周时达到峰值，然后下降。TNF-α的表达在1周时增加并持续升高。INFγ仅在对照移植物中可见。
IL-1β和bFGF的早期协同释放以及INFγ的下调似乎触发了炎症反应，从而启动了IH。然后，该过程由PDGF-AA和TNF-α的释放推动，伴随着平滑肌细胞增殖和细胞外基质的产生。很可能这种复杂的局部旁分泌信号环境是产生失败静脉移植物中所见增生反应所必需的。
