Klinik für Kardiologie und Angiologie II, Universitäts-Herzzentrum Freiburg • Bad Krozingen, Südring 15, 79189, Bad Krozingen, Germany.
J Cardiovasc Transl Res. 2013 Feb;6(1):81-93. doi: 10.1007/s12265-012-9420-5. Epub 2012 Nov 29.
Inflammation as a systemic process plays a central role in atherosclerotic plaque progression (PP). Here we investigated other systemic correlates of PP by global gene expression profiling (GEP) in peripheral blood. From a database of 45,727 coronary angiograms, we identified two patient groups with good risk factor control, but different clinical evolution: First, 16 patients had significant PP leading to repeated coronary interventions, and second, 16 patients had angiographically documented stable courses. GEP revealed 93 differentially expressed genes, of which 23 have unknown function. Among the remaining 70 genes, 10 were associated with progenitor and pluripotent cells, but only three genes with atherosclerosis. We developed a risk prediction gene signature by a multivariable statistical model integrating comprehensive laboratory and clinical patient data. This signature identified PP with high sensitivity and specificity for new patients, as estimated by resampling techniques. GEP results were validated by qPCR for ANK2 and GSTT1.
炎症作为一个全身性过程，在动脉粥样硬化斑块进展（PP）中起着核心作用。在这里，我们通过外周血的全基因组表达谱（GEP）研究了 PP 的其他全身性相关性。从一个包含 45727 例冠状动脉造影的数据库中，我们确定了两组具有良好危险因素控制但临床演变不同的患者：第一组 16 例患者有明显的 PP，导致反复冠状动脉介入治疗；第二组 16 例患者有血管造影记录的稳定病程。GEP 显示 93 个差异表达基因，其中 23 个具有未知功能。在剩下的 70 个基因中，有 10 个与祖细胞和多能细胞有关，但只有 3 个与动脉粥样硬化有关。我们通过整合全面的实验室和临床患者数据的多变量统计模型，开发了一个风险预测基因特征。通过重采样技术估计，该特征对新患者的 PP 具有较高的灵敏度和特异性。ANK2 和 GSTT1 的 qPCR 验证了 GEP 结果。
