Abstract
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.
Highlights
Hypertensive left ventricular hypertrophy (LVH) is a well-recognized risk factor for heart failure, myocardial infarction, arrhythmias, sudden cardiac death, and stroke [1, 2]
We firstly evaluated the gene expression profiles in peripheral blood leukocytes from normal individuals and hypertensive patients without LVH or with LVH based on Gene Expression Omnibus (GEO) datasets
According to the screening method and criteria discussed above, no differentially expressed genes (DEGs) were detected between Control samples and HT without LVH samples, which was consistent with the outcome of the principal component analysis (PCA) test
Summary
Hypertensive left ventricular hypertrophy (LVH) is a well-recognized risk factor for heart failure, myocardial infarction, arrhythmias, sudden cardiac death, and stroke [1, 2]. LVH can be assessed by electrocardiography (ECG), echocardiography, computed tomography (CT), and cardiac magnetic resonance imaging (CMRI). Detection of LVH is subject to various limitations, such as low sensitivity and specificity, lengthy diagnostic time, technical complexity, and expenses [3]. This has led to accelerate research on the use of circulating biomarkers as diagnostic and prognostic tools for LVH www.aging‐us.com in patients with hypertension, as it is difficult to obtain tissue biopsies. Despite the high clinical and diagnostic value of these biomarkers, more practical biomarkers are required to enhance the early detection and the diagnostic accuracy of cardiac disease.
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