Identification of Target Genes in Hypertension and Left Ventricular Remodeling

Abstract

Introduction: Hypertension occurs profoundly in the world, and left ventricular (LV) remodeling containing functional, structural, and mechanical changes induced by uncontrolled blood pressure is a well-known complication, however the underlying mechanism is still obscure. Methods: To determine differences in gene expression profiles of hypertension and LV remodeling consequence to hypertension, Gene Expression Omnibus 2R online tool was used to identify differently expressed genes. Publicly available databases including GeneMANIA, database for annotation, visualization and integrated discovery, search tool for the retrieva predicting associated transcription factors (TF) from annotated affinities interacting genes, Predicting Associated TF from Annotated Affinities, JASPAR and Comparative Toxicogenomics Database (CTD) were accessed to perform an integrated bioinformatic analysis. Results: Twenty-one genes (SEC14L3, EML7, PSMD7, PSMA1, GLRX, CNOT10, NBR1, DUSP12, STRAP, SMIM14, RBM8A, TMEM59, TMEM87A,PSMC1, CASP4, ITGB8, DNAJA1, PINK1, PRNP, SAP30L, and EIF3M) were found overexpression in both hypertension and hypertensive LV remodeling. Biological process analysis first revealed that enrichment of these target genes correlated with regulation of cellular amino acid metabolic process, antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent and proteasome complex, 3 different expression genes (DEGs) participate significantly enriched in NFκB, WNT, and MAPK pathways, meanwhile, 47% DEGs displayed similar co-expression characteristics. Furthermore, the transcription factors associated with key DEGs were identified. Finally, the TF (HAND1, E4BP4, ESR1, VBP, ELK-1, POU3F2) associated with LV remodeling in hypertension were confirmed to act a crucial role in correlated heart diseases. Conclusion: The present study reveals the targeted genes probably associated with LV remodeling in hypertension by bioinformatics-based analyses, which provides clues for prognosis judgement and pharmacological therapies.

Identification of intrinsic genes across general hypertension, hypertension with left ventricular remodeling, and uncontrolled hypertension

“…Furthermore, we identified 23 differentially expressed probes (DEGs, 2 upregulated genes, and 21 downregulated genes) in peripheral blood cell samples from the GSE74144 dataset (hypertensive patient with normal left ventricular vs. normal control), which was exhibited in Figures 3D , H . Interestingly, we detected few differentially expressed genes in the GSE75360, GSE71994, and part of the GSE74144 datasets based on an absolute 2-fold change with a p -value of < 0.05 ( Figures 3B , C , E , F ), which was contrary to that of Pang et al ( 24 ) who found that 842 DEGs were identified in the GSE71994 dataset (including 629 upregulated genes and 213 downregulated genes), while 28,232 DEGs were identified in the GSE74144 dataset. To account for that contradiction, we continued searching for different publications.…”

Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study

“…This gene codes for a subunit of the 26S proteasome complex, which is involved in protein homeostasis. In a gene network analysis, PSMD7 was upregulated in hypertensive patients with LV remodeling compared to those without LV remodeling [ 58 ]. Like GSE1 , the PSMD7 DMR has strong enhancer activity and is an alternative splicing site.…”

Deciphering the Protein, Modular Connections and Precision Medicine for Heart Failure With Preserved Ejection Fraction and Hypertension Based on TMT Quantitative Proteomics and Molecular Docking

“…Thus, COQ9 is also a potential biomarker for HTN and HFpEF. Several studies have shown that the expression of Tf and Prnp is altered in many cardiovascular diseases and that Tf and Prnp may be novel biomarkers for HTN and HFpEF ( Gao et al, 2013 ; Rahim et al, 2018 ; Roura et al, 2018 ; Pang et al, 2020 ). Acta1 is involved in the pathological progression of myocardial remodeling ( Pagano et al, 2017 ; Cañes et al, 2020 ), which is closely related to the prognosis of HTN and HFpEF ( Fortuño et al, 2001 ; Georgiopoulou et al, 2010 ; Heinzel et al, 2015 ).…”