School of Medicine, Nankai University, 300071 Tianjin, China.
Department of Heart Center, Nankai University Affiliated Third Center Hospital, 300170 Tianjin, China.
Rev Cardiovasc Med. 2022 Mar 18;23(3):109. doi: 10.31083/j.rcm2303109.
Elevated left ventricular mass index contributes to morbidity and mortality induced by heart failure and M2 macrophages play a critical role in left ventricular remodeling. Here, our aim was to investigate the roles of M2 macrophage-related genes in heart failure.
GSE10161 was downloaded and the abundance of immune cells were estimated utilizing the CIBERSORT algorithm. Using the limma test and correlation analysis, differentially expressed plasm B cells and M2 macrophages-related genes (DEBRGs and DEMRGs) were documented. Functional pathways and the protein-protein interaction network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the hub DEMRGs expressions were analyzed using the GSE135055, GSE116250 and GSE74144 datasets.
103 differentially expressed genes were correlated with the abundance of M2 Macrophages and were identified as DEMRGs (PCC >0.4), which were mainly enriched in extracellular matrix organization, cell adhesion molecule binding and postsynaptic membrane. After screening out, 5 hub DEMRGs were obtained, including FN1 (degree = 21), COL3A1 (degree = 13), COL1A2 (degree = 13), FBN1 (degree = 12), and MMP2 (degree = 11). However, no hub DEBRGs were obtained in the network. The expression patterns of the screened DEMRGs were further validated in the patients with heart failure, dilated cardiomyopathy, ischemic cardiomyopathy or hypertension.
The results can improve our understanding of the macrophages-associated molecular mechanisms in heart failure induced by dilated cardiomyopathy, ischemic cardiomyopathy or hypertension and 5 hub DEMRGs may help prevent the adverse left ventricular remodeling to decrease mortality and morbidity.
左心室质量指数升高会导致心力衰竭引起的发病率和死亡率升高,M2 巨噬细胞在左心室重构中起关键作用。本研究旨在探讨 M2 巨噬细胞相关基因在心力衰竭中的作用。
下载 GSE10161 数据集,利用 CIBERSORT 算法估计免疫细胞的丰度。采用 limma 检验和相关性分析,确定差异表达的浆细胞和 M2 巨噬细胞相关基因(DEBRGs 和 DEMRGs)。分析功能途径和蛋白质-蛋白质相互作用网络,获得关键的 DEMRGs。使用 NetworkAnalyst 3.0 分析关键的 DEMRGs 及其相互作用,并利用 GSE135055、GSE116250 和 GSE74144 数据集验证关键的 DEMRGs 表达。
有 103 个差异表达基因与 M2 巨噬细胞丰度相关,被鉴定为 DEMRGs(PCC>0.4),主要富集在外基质组织、细胞黏附分子结合和突触后膜。经过筛选,获得了 5 个关键的 DEMRGs,包括 FN1(度=21)、COL3A1(度=13)、COL1A2(度=13)、FBN1(度=12)和 MMP2(度=11)。然而,在网络中没有获得关键的 DEBRGs。进一步在心力衰竭、扩张型心肌病、缺血性心肌病或高血压患者中验证了筛选出的 DEMRGs 的表达模式。
研究结果可提高我们对扩张型心肌病、缺血性心肌病或高血压引起的心力衰竭中巨噬细胞相关分子机制的认识,5 个关键的 DEMRGs 可能有助于预防不良的左心室重构,降低死亡率和发病率。