摘要
出身背景
动脉粥样硬化（AS）是一种慢性炎症性疾病，是导致世界范围内血管疾病的主要原因。尽管越来越多的研究集中在AS中的巨噬细胞上，但其确切的相关机制仍在很大程度上不清楚。本研究旨在探讨巨噬细胞自噬相关基因（MARG）在AS中的致病作用和诊断作用。
方法
所有数据集均从基因表达综合数据库和人类自噬数据库下载。进行差异表达分析和交叉分析以确定候选MARG。进行GO和KEGG富集分析以获得功能信息。此外，我们还分析了AS中靶基因与巨噬细胞极化的相关性。还分析了靶基因与斑块不稳定性、AS不同阶段的相关性。
后果
与正常样本相比，AS样本中共鉴定出575个差异表达基因。对上述575个DEG和自噬相关基因（ARGs）进行交叉分析后，共获得12个重叠基因。然后，在AS样本中鉴定出10个MARG，它们在22个KEGG途径和61个GO术语中显著富集。与正常样本相比，动脉粥样硬化样本中HSPB8的表达显著下调（变化最大）。同时，低HSPB8表达AS组的M-CSF比例高于高表达AS组。此外，HSPB8的表达与大多数炎症因子呈负相关。
结论
MARG HSPB8的下调可能与AS样品中M2巨噬细胞的极化有关。HSPB8是AS患者一种很有前途的诊断标志物。
Abstract
Background
Atherosclerosis (AS) is a chronic inflammatory disease, as a main cause leading to vascular diseases worldwide. Although increasing studies have focused on macrophages in AS, the exact relating mechanism is still largely unclear. Our study aimed to explore the pathogenic role and diagnostic role of macrophage autophagy related genes (MARGs) in AS.

Methods
All datasets were downloaded from Gene Expression Omnibus database and Human Autophagy Database. The differential expression analysis and cross analysis were performed to identify candidate MARGs. GO and KEGG enrichment analyses were conducted to obtain the functional information. Moreover, we analyzed the correlation between target gene and macrophage polarization in AS. The correlation between target gene and plaque instability, different stages of AS were also analyzed.

Results
Compared with normal samples, a total of 575 differentially expressed genes (DEGs) were identified in AS samples. A total of 12 overlapped genes were obtained after cross-analysis of the above 575 DEGs and autophagy related genes (ARGs). Then, 10 MARGs were identified in AS samples, which were significantly enriched in 22 KEGG pathways and 61 GO terms. The expression of HSPB8 was significantly down-regulated in atherosclerotic samples compared with normal samples (with largest fold change). Meanwhile, the proportion of M-CSF in low HSPB8 expression AS group was higher than high expression AS group. Furthermore, the expression of HSPB8 was negatively correlated with most inflammatory factors.

Conclusion
The downregulation of MARG HSPB8 probably involves in the M2 macrophage polarization in AS samples. HSPB8 is a promising diagnostic marker for AS patients.

https://link.springer.com/article/10.1186/s12872-023-03158-2