State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Aging (Albany NY). 2022 Feb 14;14(3):1508-1528. doi: 10.18632/aging.203894.
Left ventricular hypertrophy (LVH) is a pivotal manifestation of hypertensive organ damage associated with an increased cardiovascular risk. However, early diagnostic biomarkers for assessing LVH in patients with hypertension (HT) remain indefinite. Here, multiple bioinformatics tools combined with an experimental verification strategy were used to identify blood biomarkers for hypertensive LVH. GSE74144 mRNA expression profiles were downloaded from the Gene Expression Omnibus (GEO) database to screen candidate biomarkers, which were used to perform weighted gene co-expression network analysis (WGCNA) and establish the least absolute shrinkage and selection operator (LASSO) regression model, combined with support vector machine-recursive feature elimination (SVM-RFE) algorithms. Finally, the potential blood biomarkers were verified in an animal model. A total of 142 hub genes in peripheral blood leukocytes were identified between HT with LVH and HT without LVH, which were mainly involved in the ATP metabolic process, oxidative phosphorylation, and mitochondrial structure and function. Notably, lysosomal associated transmembrane protein 5 (LAPTM5) was identified as the potential diagnostic marker of hypertensive LVH, which showed strong correlations with diverse marker sets of reactive oxygen species (ROS) and autophagy. RT-PCR validation of blood samples and cardiac magnetic resonance imaging (CMRI) showed that the expression of LAPTM5 was significantly higher in the HT with LVH model than in normal controls, LAPTM5 demonstrated a positive association with the left ventricle wall thickness as well as electrocardiogram (ECG) parameters widths of the QRS complex and QTc interval. In conclusion, LAPTM5 may be a potential biomarker for the diagnosis of LVH in patients with HT, and it can provide new insights for future studies on the occurrence and the molecular mechanisms of hypertensive LVH.
左心室肥厚（LVH）是高血压相关器官损害的主要表现之一，与心血管风险增加相关。然而，评估高血压患者 LVH 的早期诊断生物标志物仍不明确。在这里，我们采用多种生物信息学工具并结合实验验证策略，以确定高血压性 LVH 的血液生物标志物。从基因表达综合数据库（GEO）下载 GSE74144mRNA 表达谱，筛选候选生物标志物，用于进行加权基因共表达网络分析（WGCNA）和建立最小绝对收缩和选择算子（LASSO）回归模型，并结合支持向量机递归特征消除（SVM-RFE）算法。最后，在动物模型中验证潜在的血液生物标志物。在 HT 伴 LVH 和 HT 不伴 LVH 的外周血白细胞中鉴定出 142 个核心基因，这些基因主要参与三磷酸腺苷代谢过程、氧化磷酸化和线粒体结构与功能。值得注意的是，溶酶体相关跨膜蛋白 5（LAPTM5）被鉴定为高血压性 LVH 的潜在诊断标志物，其与多种活性氧（ROS）和自噬标志物集显示出强烈相关性。对血液样本的 RT-PCR 验证和心脏磁共振成像（CMRI）显示，HT 伴 LVH 模型中的 LAPTM5 表达明显高于正常对照组，LAPTM5 与左心室壁厚度以及心电图（ECG）参数 QRS 复合波和 QTc 间期的宽度呈正相关。总之，LAPTM5 可能是高血压患者 LVH 诊断的潜在生物标志物，为高血压性 LVH 的发生和分子机制的未来研究提供了新的见解。
