DeSart Kenneth, O'Malley Kerri, Schmit Bradley, Lopez Maria-Cecilia, Moldawer Lyle, Baker Henry, Berceli Scott, Nelson Peter
Department of Surgery, University of Florida College of Medicine, Gainesville, Fla.
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Fla.
J Vasc Surg. 2016 Sep;64(3):766-778.e5. doi: 10.1016/j.jvs.2015.04.399. Epub 2015 Jun 6.
The activation state of the systemic inflammatory milieu has been proposed as a critical regulator of vascular repair after injury. We evaluated the early inflammatory response after endovascular intervention for symptomatic peripheral arterial disease to determine its association with clinical success or failure.
Blood samples were obtained from 14 patients undergoing lower extremity angioplasty/stenting and analyzed using high-throughput gene arrays, multiplex serum protein analyses, and flow cytometry.
Time-dependent plasma protein and monocyte phenotype analyses demonstrated endovascular revascularization had a modest influence on the overall activation state of the systemic inflammatory system, with baseline variability exceeding the perturbations induced by the intervention. In contrast, specific time-dependent changes in the monocyte genome are evident in the initial 28 days, predominately in those genes associated with leukocyte extravasation. Investigating the relationship between inflammation and the 1-year success or failure of the intervention showed no single plasma protein was correlated with outcome, but a more comprehensive cluster analysis revealed a clear pattern of protein expression that was closely related to the clinical phenotype. Corresponding examination of the monocyte genome identified a gene subset at 1 day postprocedure that was predictive of clinical outcome, with most of these genes active in cell-cycle signaling.
Although the global influence of angioplasty/stenting on systemic inflammation was modest, circulating cytokine and monocyte genome analyses support a pattern of early inflammation that is associated with ultimate intervention success vs failure. Molecular profiles incorporating genes involved in monocyte cell-cycle progression and homing, or proinflammatory cytokines, or both, offer the most promise for the development of class prediction tools for clinical application.
全身炎症环境的激活状态被认为是损伤后血管修复的关键调节因子。我们评估了有症状外周动脉疾病血管内介入治疗后的早期炎症反应，以确定其与临床成功或失败的关联。
从14例行下肢血管成形术/支架置入术的患者中采集血样，并用高通量基因芯片、多重血清蛋白分析和流式细胞术进行分析。
血浆蛋白和单核细胞表型的时间依赖性分析表明，血管内血运重建对全身炎症系统的整体激活状态影响不大，基线变异性超过了干预引起的扰动。相比之下，单核细胞基因组在最初28天有明显的特定时间依赖性变化，主要发生在与白细胞外渗相关的基因中。研究炎症与干预1年成功或失败之间的关系发现，没有单一血浆蛋白与结果相关，但更全面的聚类分析揭示了一种与临床表型密切相关的蛋白表达模式。对单核细胞基因组的相应检查在术后1天确定了一个预测临床结果的基因子集，这些基因大多在细胞周期信号传导中活跃。
尽管血管成形术/支架置入术对全身炎症的总体影响不大，但循环细胞因子和单核细胞基因组分析支持一种与最终干预成功或失败相关的早期炎症模式。纳入参与单核细胞细胞周期进程和归巢的基因或促炎细胞因子或两者的分子谱，为开发临床应用的分类预测工具提供了最大希望。
