Li Zhetao, Zhao Wansong, Ji Wenbo, Li Zhaoshui, Wang Kuo, Jiang Ting
Heart Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People's Republic of China.
Operating Room Department, Qingdao Municipal Hospital, Qingdao, People's Republic of China.
J Inflamm Res. 2024 Nov 28;17:9925-9951. doi: 10.2147/JIR.S489847. eCollection 2024.
Coronary atherosclerosis (CA) is a major cause of coronary artery disease (CHD), with inflammation significantly influencing its pathogenesis. This study explores the role of neutrophil extracellular traps (NETs) in CA to understand their influence on disease progression.
Using the GEO database, we analyzed RNA expression microarray data from CA patients, identifying NET-related differentially expressed genes (NETDEGs) through logistic regression, SVM, and LASSO operator regression analyses. CA samples were categorized into risk subgroups based on gene traits, with further analysis on the biological characteristics and immune cell infiltration of the high-risk subgroup. Additionally, transcription factor (TF)-gene, microRNA (miRNA)-gene, and RNA binding protein (RBP)-gene regulatory networks were investigated, alongside a protein-drug network to propose potential targeting therapies. Expression levels of NETDEGs were validated via qRT-PCR and Western blotting.
Three NETDEGs-MMP9, ERN1, and G0S2-were pinpointed as key players in CA development, regulated by TFs, miRNAs, and RBPs. These genes defined high-risk subgroups marked by intense inflammatory signaling and apoptosis. High neutrophil infiltration correlated positively with NETDEG expression in CA samples, supporting their potential as biomarkers. MMP9 emerged as a notable drug target, providing a possible therapeutic avenue.
This research highlights an independent NETDEG trait in CA, offering insights into potential biomarkers and therapeutic targets for combating this disease.
冠状动脉粥样硬化（CA）是冠状动脉疾病（CHD）的主要病因，炎症对其发病机制有显著影响。本研究探讨中性粒细胞胞外陷阱（NETs）在CA中的作用，以了解它们对疾病进展的影响。
利用GEO数据库，我们分析了CA患者的RNA表达微阵列数据，通过逻辑回归、支持向量机和套索算子回归分析确定与NET相关的差异表达基因（NETDEGs）。根据基因特征将CA样本分为风险亚组，并对高风险亚组的生物学特征和免疫细胞浸润进行进一步分析。此外，还研究了转录因子（TF）-基因、微小RNA（miRNA）-基因和RNA结合蛋白（RBP）-基因调控网络，以及蛋白质-药物网络，以提出潜在的靶向治疗方法。通过qRT-PCR和蛋白质免疫印迹法验证NETDEGs的表达水平。
确定了三个NETDEGs——基质金属蛋白酶9（MMP9）、内质网应激反应蛋白1（ERN1）和G0/G1开关2（G0S2）——是CA发展的关键因素，它们受TFs、miRNAs和RBPs的调控。这些基因定义了以强烈炎症信号和细胞凋亡为特征的高风险亚组。在CA样本中，高嗜中性粒细胞浸润与NETDEG表达呈正相关，支持它们作为生物标志物的潜力。MMP9成为一个值得注意的药物靶点，为治疗提供了一条可能的途径。
本研究突出了CA中一个独立的NETDEG特征，为对抗这种疾病的潜在生物标志物和治疗靶点提供了见解。
