Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Chaoyang 100029, Beijing, China.
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping 102218, Beijing, China.
Aging (Albany NY). 2024 May 9;16(9):8260-8278. doi: 10.18632/aging.205816.
Myocardial fibrosis is an important pathological change that occurs during ventricular remodeling in patients with hypertension and is an important pathophysiological basis of cardiovascular disease. However, the molecular mechanism underlying this ventricular remodeling is unclear.
Bioinformatics analysis identified HLA-B and TIMP1 as hub genes in the process of myocardial fibrosis. Expression and correlation analyses of significant hub genes with ventricular remodeling were performed. Weighted gene co-expression network analysis (WGCNA) was performed to verify the role of HLA-B. ceRNA network was constructed to identify the candidate molecule drugs. Receiver operating characteristic (ROC) curves were analyzed.
RT-qPCR was performed to verify the roles of HLA-B and TIMP1 in seven control individuals with hypertension and seven patients with hypertension and ventricular remodeling. The WGCNA showed that HLA-B was in the brown module and the correlation coefficient between HLA-B and ventricular remodeling was 0.67. Based on univariate logistic proportional regression analysis, HLA-B influences ventricular remodeling (P<0.05). RT-qPCR showed that the relative expression levels of HLA-B and TIMP1 were significantly higher in HLVR samples compared with their expression in the control group.
HLA-B and TIMP1 might provide novel research targets for the diagnosis and treatment of HLVR.
心肌纤维化是高血压患者心室重构过程中发生的重要病理改变，也是心血管疾病的重要病理生理基础。然而，这种心室重构的分子机制尚不清楚。
生物信息学分析确定 HLA-B 和 TIMP1 是心肌纤维化过程中的枢纽基因。对显著枢纽基因与心室重构的表达和相关性进行分析。进行加权基因共表达网络分析（WGCNA）以验证 HLA-B 的作用。构建 ceRNA 网络以鉴定候选分子药物。分析接收者操作特征（ROC）曲线。
进行 RT-qPCR 以验证 HLA-B 和 TIMP1 在 7 名高血压对照个体和 7 名高血压伴心室重构患者中的作用。WGCNA 显示 HLA-B 位于棕色模块，HLA-B 与心室重构之间的相关系数为 0.67。基于单变量逻辑比例回归分析，HLA-B 影响心室重构（P<0.05）。RT-qPCR 显示 HLVR 样本中 HLA-B 和 TIMP1 的相对表达水平明显高于对照组。
HLA-B 和 TIMP1 可能为 HLVR 的诊断和治疗提供新的研究靶点。
