Transcriptomic signatures of atheroresistance in the human atrium and ventricle highlight potential candidates for targeted atherosclerosis therapeutics

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Paul A. Brown
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Abstract

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.
人类心房和心室动脉粥样硬化抵抗的转录组学特征突出了靶向动脉粥样硬化治疗的潜在候选者
动脉粥样硬化的风险在整个心血管系统中并不均匀。因此,本研究旨在比较动脉粥样硬化抵抗的人类心房和心室与动脉粥样硬化倾向的冠状动脉的转录组,以确定动脉粥样硬化抵抗的转录组特征和动脉粥样硬化治疗的潜在靶点。利用公开可用的基因读取计数,鉴定出心房、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,过度代表性分析和主动子网导向的富集评估确定了富集的术语,并将其归类为内皮功能障碍相关过程。通过通路分析进一步探讨潜在的生物学意义。在21474个特征中,在三个对比中鉴定出12656个差异表达基因,并与1215个富集项相关。在整个对比中,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相关,包括免疫调节剂、细胞粘附分子、脂质代谢和凝固相关分子。差异表达基因与京都基因与基因组百科全书中6条下调通路相关,与免疫细胞和相关内皮细胞功能相关。回顾与内皮功能障碍相关过程相关的调控基因,并包括在这些途径中,表明免疫细胞相关的B细胞支架蛋白与锚蛋白重复序列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,是潜在的动脉粥样硬化靶点。
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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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