Qin Ming, Chen Qian, Li Ning, Xu Xiangyang, Wang Chuyi, Wang Guokun, Xu Zhiyun
Department of Cardiovascular Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Cardiothoracic Surgery, People's Liberation Army Navy Medical Center, Naval Medical University, Shanghai, China.
Front Cardiovasc Med. 2023 Jan 4;9:1058274. doi: 10.3389/fcvm.2022.1058274. eCollection 2022.
CAVD is a common cardiovascular disease, but currently there is no drug treatment. Therefore, it is urgent to find new and effective drug therapeutic targets. Recent evidence has shown that the infiltration of M1 macrophages increased in the calcified aortic valve tissues, but the mechanism has not been fully elucidated. The purpose of this study was to explore the shared gene characteristics and molecular mechanisms of macrophages M1 polarization in CAVD, in order to provide a theoretical basis for new drugs of CAVD.
The mRNA datasets of CAVD and M1 polarization were downloaded from Gene Expression Omnibus (GEO) database. R language, String, and Cytoscape were used to analyze the functions and pathways of DEGs and feature genes. Immunohistochemical staining and Western Blot were performed to verify the selected hub genes.
CCR7 and GZMB were two genes appeared together in hub genes of M1-polarized and CAVD datasets that might be involved in the process of CAVD and macrophages M1 polarization. CCR7 and CD86 were significantly increased, while CD163 was significantly decreased in the calcified aortic valve tissues. The infiltration of M1 macrophages was increased, on the contrary, the infiltration of M2 macrophages was decreased in the calcified aortic valve tissues.
This study reveals the shared gene characteristics and molecular mechanisms of CAVD and macrophages M1 polarization. The hub genes and pathways we found may provide new ideas for the mechanisms underlying the occurrence of M1 polarization during CAVD process.
钙化性主动脉瓣疾病（CAVD）是一种常见的心血管疾病，但目前尚无药物治疗方法。因此，迫切需要寻找新的有效药物治疗靶点。最近的证据表明，钙化主动脉瓣组织中M1巨噬细胞的浸润增加，但其机制尚未完全阐明。本研究的目的是探讨CAVD中巨噬细胞M1极化的共同基因特征和分子机制，为CAVD的新药研发提供理论依据。
从基因表达综合数据库（GEO）下载CAVD和M1极化的mRNA数据集。使用R语言、String和Cytoscape分析差异表达基因（DEGs）和特征基因的功能及通路。进行免疫组织化学染色和蛋白质印迹法验证所选的枢纽基因。
趋化因子受体7（CCR7）和颗粒酶B（GZMB）是在M1极化和CAVD数据集的枢纽基因中共同出现的两个基因，可能参与CAVD和巨噬细胞M1极化过程。在钙化主动脉瓣组织中，CCR7和CD86显著增加，而CD163显著降低。钙化主动脉瓣组织中M1巨噬细胞的浸润增加，相反，M2巨噬细胞的浸润减少。
本研究揭示了CAVD和巨噬细胞M1极化的共同基因特征和分子机制。我们发现的枢纽基因和通路可能为CAVD过程中M1极化发生的机制提供新的思路。
