Brown Paul A
Department of Basic Medical Sciences, Faculty of Medical Sciences Teaching and Research Complex, The University of the West Indies, Mona, Kingston 7, Jamaica.
Biochem Biophys Rep. 2025 Apr 8;42:102007. doi: 10.1016/j.bbrep.2025.102007. eCollection 2025 Jun.
Atherosclerosis risk is not uniform throughout the cardiovascular system. This study therefore aimed to compare the transcriptomes of atheroresistant human atrium and ventricle with atheroprone coronary arteries to identify transcriptomic signatures of atheroresistance and potential targets for atherosclerosis therapeutics. Using publicly available gene read counts, differentially expressed genes between the atrium, ventricle, and coronary artery were identified for each contrast and validated against the Swiss Institute of Bioinformatics' Bgee database. Over-representation analysis and active-subnetwork-oriented enrichment assessment then identified enriched terms, which were grouped into endothelial dysfunction-related processes. Potential biological significance was further explored with pathway analysis. Among 21474 features, 12656 differentially expressed genes were identified across the three contrasts and associated with 1215 enriched terms. There were 315 down-regulated and 133 up-regulated genes associated with endothelial dysfunction-related processes across the contrasts, including immune modulators, cell adhesion molecules, and lipid metabolism- and coagulation-related molecules. Differentially expressed genes were associated with six down-regulated Kyoto Encyclopedia of Genes and Genomes pathways, related to immune cell and associated endothelium functions. Review of regulated genes associated with endothelial dysfunction-related processes and included in these pathways, indicate immune cell-associated B cell scaffold protein with ankyrin repeats 1, as well as arterial endothelial cell-associated vascular cell adhesion molecule 1 and cadherin 5, as potential atherosclerosis targets.
动脉粥样硬化风险在整个心血管系统中并不均匀。因此，本研究旨在比较抗动脉粥样硬化的人类心房和心室与易发生动脉粥样硬化的冠状动脉的转录组，以确定抗动脉粥样硬化的转录组特征以及动脉粥样硬化治疗的潜在靶点。利用公开可用的基因读数，针对每种对比确定心房、心室和冠状动脉之间的差异表达基因，并根据瑞士生物信息学研究所的Bgee数据库进行验证。然后，通过过度表达分析和面向活性子网的富集评估来确定富集术语，这些术语被归类为与内皮功能障碍相关的过程。通过通路分析进一步探索潜在的生物学意义。在21474个特征中，在三种对比中鉴定出12656个差异表达基因，并与1215个富集术语相关联。在这些对比中，有315个下调基因和133个上调基因与内皮功能障碍相关过程有关，包括免疫调节剂、细胞粘附分子以及脂质代谢和凝血相关分子。差异表达基因与六个下调的京都基因与基因组百科全书通路相关，这些通路与免疫细胞和相关内皮功能有关。对与内皮功能障碍相关过程相关且包含在这些通路中的调控基因进行审查，表明具有锚蛋白重复序列的免疫细胞相关B细胞支架蛋白1，以及动脉内皮细胞相关的血管细胞粘附分子1和钙粘蛋白5，作为潜在的动脉粥样硬化靶点。
