Zhang Peng, Lin Hui, Guo Yan, Peng Fang, Meng Liping
Department of Cardiology, Shaoxing People's Hospital, Shaoxing, Zhejiang, 312000, People's Republic of China.
Department of Cardiology, Zhuji hospital of Traditional Chinese Medicine, Shaoxing, Zhejiang, People's Republic of China.
J Inflamm Res. 2023 Oct 18;16:4713-4724. doi: 10.2147/JIR.S429247. eCollection 2023.
Atherosclerosis is still a global public problem with increasing incidence rate and mortality. It has been found that gender factors play an important role in the progression of atherosclerosis. However, few people explore gender related atherosclerosis at the level of genes and immune cells. The purpose of this study was to determine genetic and immune cell differences between male and female samples.
This study aims to identify differential genes between male and female samples in the GSE43292 dataset. The focus will be on identifying immune-related genes (IRGs) among these differentially expressed genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis will be employed to explore the enrichment of IRGs in biological processes, molecular functions, cellular components, and pathways. Furthermore, a protein-protein interaction (PPI) network for the IRGs will be constructed using Cytoscape software. To estimate the degree of immune cell infiltration, single-sample gene set enrichment analysis (ssGSEA) will be conducted. Moreover, the identified IRGs will be validated using GSE28829 dataset. Finally, we validated in atherosclerotic mice.
Seven IRGs (CCL13, IL1RN, FPR2, S100A8, CCL19, CXCL1, CXCL8) were identified as being overexpressed in male atherosclerosis. GO and KEGG analysis revealed that these IRGs are primarily enriched in inflammatory response pathways, cytokine signaling pathways, and cytokine- cytokine receptor interactions. Notably, when compared to females, there was a significant infiltration of immune cells in male specimens. Importantly, all seven IRGs demonstrated high diagnostic value in GSE28829 dataset. The use of animal samples supports our results.
This study demonstrates the effectiveness of seven IRGs and reveal sex differences in atherosclerosis. Notably, there is a significant presence of immune cells within the atherosclerotic plaque of men compared to women. These findings have potential implications for the development of personalized treatment approaches targeting gender-related atherosclerosis.
动脉粥样硬化仍是一个全球性公共问题，其发病率和死亡率不断上升。已发现性别因素在动脉粥样硬化进展中起重要作用。然而，很少有人在基因和免疫细胞水平上探讨与性别相关的动脉粥样硬化。本研究的目的是确定男性和女性样本之间的基因和免疫细胞差异。
本研究旨在识别GSE43292数据集中男性和女性样本之间的差异基因。重点将是在这些差异表达基因中识别免疫相关基因（IRGs）。随后，将采用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析来探索IRGs在生物过程、分子功能、细胞成分和通路中的富集情况。此外，将使用Cytoscape软件构建IRGs的蛋白质-蛋白质相互作用（PPI）网络。为了估计免疫细胞浸润程度，将进行单样本基因集富集分析（ssGSEA）。此外，将使用GSE28829数据集验证所识别的IRGs。最后，我们在动脉粥样硬化小鼠中进行了验证。
七个IRGs（CCL13、IL1RN、FPR2、S100A8、CCL19、CXCL1、CXCL8）被确定在男性动脉粥样硬化中过表达。GO和KEGG分析表明，这些IRGs主要富集在炎症反应通路、细胞因子信号通路和细胞因子-细胞因子受体相互作用中。值得注意的是，与女性相比，男性样本中免疫细胞有显著浸润。重要的是，所有七个IRGs在GSE28829数据集中都显示出高诊断价值。动物样本的使用支持了我们的结果。
本研究证明了七个IRGs的有效性，并揭示了动脉粥样硬化中的性别差异。值得注意的是，与女性相比，男性动脉粥样硬化斑块中免疫细胞大量存在。这些发现对针对与性别相关的动脉粥样硬化的个性化治疗方法的开发具有潜在意义。
