Prediction of marker genes associated with hypertension by bioinformatics analyses

Gao, Yuan; Qi, Guoxian; Jia, Zhang; Sun, Yingxian

doi:10.3892/ijmm.2017.3000

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…[ 41 ] The expression level of ESR1 is positively correlated with the occurrence rate of cardiovascular diseases, especially hypertension differs between males and females. [ 42 ] Mount of evidence suggests that in postmenopausal women, estrogen deficiency plays major roles in the pathogenesis of cardiovascular diseases. [ 43 ] Our findings provided basis for further exploring the application of gene target as a novel hypertension treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification of Target Genes in Hypertension and Left Ventricular Remodeling

Pang

et al. 2020

Medicine

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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.

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Section: Discussionmentioning

confidence: 99%

Identification of Target Genes in Hypertension and Left Ventricular Remodeling

Pang

et al. 2020

Medicine

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“…A further analysis revealed that BPH/2 mice have shorter telomeres, but this occurs after hypertension is established and is a consequence rather than a cause of the hypertension (Chiu et al, 2016). Other bio-informatic analyses of the Chiu et al dataset have been made by Gao et al (2017) and further novel uses of meta-genome data have suggested transcriptome networks associated with hypertension, so providing scope for new therapeutic targets (Zubcevic et al, 2017). A more recent transcriptome analysis of cardiac endothelial cells suggested that differences between prehypertensive and hypertensive adult BPH/2 mice are related to fibrosis (Nelson et al, 2018).…”

Section: Molecular Contributions To Hypertension In Bph/2 Micementioning

confidence: 99%

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

et al. 2019

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It has been 45 years since Gunther Schlager used a cross breeding program in mice to develop inbred strains with high, normal, and low blood pressure (BPH/2, BPN/3, and BPL/1 respectively). Thus, it is timely to gather together the studies that have characterized and explored the mechanisms associated with the hypertension to take stock of exactly what is known and what remains to be determined. Growing evidence supports the notion that the mechanism of hypertension in BPH/2 mice is predominantly neurogenic with some of the early studies showing aberrant brain noradrenaline levels in BPH/2 compared with BPN/3. Analysis of the adrenal gland using microarray suggested an association with the activity of the sympathetic nervous system. Indeed, in support of this, there is a larger depressor response to ganglion blockade, which reduced blood pressure in BPH/2 mice to the same level as BPN/3 mice. Greater renal tyrosine hydroxylase staining and greater renal noradrenaline levels in BPH/2 mice suggest sympathetic hyperinnervation of the kidney. Renal denervation markedly reduced the blood pressure in BPH/2 but not BPN/3 mice, confirming the importance of renal sympathetic nervous activity contributing to the hypertension. Further, there is an important contribution to the hypertension from miR-181a and renal renin in this strain. BPH/2 mice also display greater neuronal activity of amygdalo-hypothalamic cardiovascular regulatory regions. Lesions of the medial nucleus of the amygdala reduced the hypertension in BPH/2 mice and abolished the strain difference in the effect of ganglion blockade, suggesting a sympathetic mechanism. Further studies suggest that aberrant GABAergic inhibition may play a role since BPH/2 mice have low GABAA receptor δ, α4 and β2 subunit mRNA expression in the hypothalamus, which are predominantly involved in promoting tonic neuronal inhibition. Allopregnanolone, an allosteric modulator of GABAA receptors, which increase the expression of these subunits in the amygdala and hypothalamus, is shown to reduce the hypertension and sympathetic nervous system contribution in BPH/2 mice. Thus far, evidence suggests that BPH/2 mice have aberrant GABAergic inhibition, which drives neuronal overactivity within amygdalo-hypothalamic brain regions. This overactivity is responsible for the greater sympathetic contribution to the hypertension in BPH/2 mice, thus making this an ideal model of neurogenic hypertension.

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“…Recently, LOXL2 emerged as one of the candidate genes in genome-wide association studies focused on hypertension and arterial stiffness (15,19). Additional bioinformatics analysis also identified LOXL2 as a putative marker gene in hypertension (10). LOXL2 is a member of the copper-dependent amine oxidase gene family.…”

Section: Introductionmentioning

confidence: 99%

Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening

Steppan

Wang

Bergman

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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Vascular stiffening and its sequelae are major causes of morbidity and mortality in the elderly. The increasingly accepted concept of “smooth muscle cell (SMC) stiffness syndrome” along with matrix deposition has emerged in vascular biology to account for the mechanical phenotype of arterial aging, but the molecular targets remain elusive. In this study, using an unbiased proteomic analysis, we identified lysyl oxidase-like 2 (LOXL2) as a critical SMC mediator for age-associated vascular stiffening. We tested the hypothesis that loss of LOXL2 function is protective in aging-associated vascular stiffening. We determined that exogenous and endogenous nitric oxide markedly decreased LOXL2 abundance and activity in the extracellular matrix of isolated SMCs and LOXL2 endothelial cells suppress LOXL2 abundance in the aorta. In a longitudinal study, LOXL2+/− mice were protected from age-associated increase in pulse-wave velocity, an index of vascular stiffening, as occurred in littermate wild-type mice. Using isolated aortic segments, we found that LOXL2 mediates vascular stiffening in aging by promoting SMC stiffness, augmented SMC contractility, and vascular matrix deposition. Together, these studies establish LOXL2 as a nodal point for a new therapeutic approach to treat age-associated vascular stiffening. NEW & NOTEWORTHY Increased central vascular stiffness augments risk of major adverse cardiovascular events. Despite significant advances in understanding the genetic and molecular underpinnings of vascular stiffening, targeted therapy has remained elusive. Here, we show that lysyl oxidase-like 2 (LOXL2) drives vascular stiffening during aging by promoting matrix remodeling and vascular smooth muscle cell stiffening. Reduced LOXL2 expression protects mice from age-associated vascular stiffening and delays the onset of isolated systolic hypertension, a major consequence of stiffening.

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Prediction of marker genes associated with hypertension by bioinformatics analyses

Cited by 7 publications

References 48 publications

Identification of Target Genes in Hypertension and Left Ventricular Remodeling

Identification of Target Genes in Hypertension and Left Ventricular Remodeling

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening

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