Comprehensive bioinformatics analysis identifies LAPTM5 as a potential blood biomarker for hypertensive patients with left ventricular hypertrophy

左心室肥大 心室 生物标志物 内科学 医学 心脏病学 Lasso(编程语言) 磁共振成像 肌肉肥大 生物信息学 血压 生物 计算机科学 放射科 生物化学 万维网
作者
Tiegang Li,Weiqi Wang,Wenxia Gan,Silin Lv,Zheng-pei Zeng,Yufang Hou,Yan Zheng,Rixin Zhang,Min Yang
出处
期刊:Aging [Impact Journals LLC]
卷期号:14 (3): 1508-1528 被引量:11
标识
DOI:10.18632/aging.203894
摘要

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.

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