Wang Kangjie, Ye Yanchen, Huang Lin, Wu Ridong, He Rongzhou, Yao Chen, Wang Shenming
Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Cardiovasc Med. 2022 Jul 6;9:954283. doi: 10.3389/fcvm.2022.954283. eCollection 2022.
Arteriosclerosis obliterans (ASO) is a limb manifestation of large vessel atherosclerosis. Phenotype switching of vascular smooth muscle cells (VSMCs) occurs in the course of the pathological process. The underlying mechanism of SMCs proliferation remains unclear. Several studies have demonstrated that the dysregulation of long non-coding RNA (lncRNAs) plays a pivotal part in the progression of ASO by exacerbating the proliferation of VSMCs. Based on the endogenous competitive RNA (ceRNA) hypothesis, the mechanism of lncRNAs involved in the pathology of VSMCs was exposed, while the entire map of the regulatory network remains to be elucidated. In the current study, genes and the lncRNAs modules that are relevant to the clinical trait were confirmed through weighted gene co-expression network analysis (WGCNA). In this study, we comprehensively constructed a specific lncRNAs-mediated ceRNA and RBP network. The three lncRNAs, , and , influenced the proliferation of VSMCs and were found to be associated with the immune landscape, thus they were ultimately screened out. Further verification revealed that was significantly down-regulated in both ASO arteries and all stages of proliferative VSMCs, which implied that might have a significant impact on ASO. This finding would improve our understanding of the epigenetic regulation of ASO and unravel novel diagnostic and therapeutic targets.
闭塞性动脉硬化（ASO）是大血管动脉粥样硬化的肢体表现。血管平滑肌细胞（VSMC）的表型转换发生在病理过程中。平滑肌细胞增殖的潜在机制仍不清楚。多项研究表明，长链非编码RNA（lncRNA）的失调通过加剧VSMC的增殖在ASO的进展中起关键作用。基于内源性竞争RNA（ceRNA）假说，lncRNA参与VSMC病理的机制得以揭示，而调控网络的全貌仍有待阐明。在本研究中，通过加权基因共表达网络分析（WGCNA）确定了与临床特征相关的基因和lncRNA模块。在本研究中，我们全面构建了一个特定的lncRNA介导的ceRNA和RBP网络。三种lncRNA，即[具体名称1]、[具体名称2]和[具体名称3]，影响VSMC的增殖，并被发现与免疫格局相关，因此最终被筛选出来。进一步验证发现，[具体名称1]在ASO动脉和增殖性VSMC的所有阶段均显著下调，这表明[具体名称1]可能对ASO有重大影响。这一发现将增进我们对ASO表观遗传调控的理解，并揭示新的诊断和治疗靶点。
