Behrens Amelie L, Dihlmann Susanne, Grond-Ginsbach Caspar, Peters Andreas S, Dorweiler Bernhard, Böckler Dittmar, Erhart Philipp
Department of Vascular and Endovascular Surgery, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Department of Vascular and Endovascular Surgery, University Hospital Cologne, 50937 Köln, Germany.
J Clin Med. 2022 Jun 7;11(12):3260. doi: 10.3390/jcm11123260.
Gene expression profiling of abdominal aortic aneurysms (AAA) indicates that chronic inflammatory responses, active matrix metalloproteinases, and degradation of the extracellular matrix components are involved in disease development and progression. This study investigates intra- and interpersonal RNA genome-wide expression profiling differences (Illumina HumanHT-12, BeadCHIP expression) of 24 AAA biopsies from 12 patients using a single gene and pathway (GeneOntology, GO enrichment) analysis. Biopsies were collected during open surgical AAA repair and according to prior finite element analysis (FEA) from regions with the highest and lowest wall stress. Single gene analysis revealed a strong heterogeneity of RNA expression parameters within the same and different AAA biopsies. The pathway analysis of all samples showed significant enrichment of genes from three different signaling pathways (integrin signaling pathway: fold change FC 1.63, = 0.001; cholecystokinin receptor pathway: FC 1.60, = 0.011; inflammation mediated by chemokine signaling pathway: FC 1.45, = 0.028). These results indicate heterogeneous gene expression patterns within the AAA vascular wall. Single biopsy investigations do not permit a comprehensive characterization of activated molecular processes in AAA disease.
腹主动脉瘤（AAA）的基因表达谱分析表明，慢性炎症反应、活性基质金属蛋白酶以及细胞外基质成分的降解参与了疾病的发生和发展。本研究使用单基因和通路（基因本体论，GO富集）分析，调查了12例患者的24份AAA活检样本在个体内和个体间的全基因组RNA表达谱差异（Illumina HumanHT-12，BeadCHIP表达）。活检样本在开放性手术AAA修复过程中收集，并根据先前的有限元分析（FEA），从壁应力最高和最低的区域获取。单基因分析显示，同一AAA活检样本内以及不同AAA活检样本间的RNA表达参数存在很强的异质性。对所有样本的通路分析表明，来自三种不同信号通路的基因有显著富集（整合素信号通路：倍数变化FC 1.63，P = 0.001；胆囊收缩素受体通路：FC 1.60，P = 0.011；趋化因子信号通路介导的炎症：FC 1.45，P = 0.028）。这些结果表明AAA血管壁内存在异质性基因表达模式。单次活检研究无法全面表征AAA疾病中激活的分子过程。
