scholarly journals A meta-analysis of Microarray Data is Effective for Identifying Gravity-Sensitive Genes

2021 ◽  
Author(s):  
Yin Liang ◽  
Mengxue Wang ◽  
Yun Liu ◽  
Chen Wang ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Candidate Genes ◽  
Dna Microarray ◽  
Meta Analysis ◽  
Vascular Endothelial Cell ◽  
Gene Expression Pattern ◽  
Expression Level ◽  
Vascular Endothelial ◽  
Microarray Datasets

AbstractGravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells to simulated microgravity using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin transporter gene SLCO2A1 decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level of SLCO2A1, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.

scholarly journals Meta-Analysis-Assisted Detection of Gravity-Sensitive Genes in Human Vascular Endothelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yin Liang ◽  
Mengxue Wang ◽  
Yun Liu ◽  
Chen Wang ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Candidate Genes ◽  
Dna Microarray ◽  
Vascular Endothelial Cells ◽  
Meta Analysis ◽  
Vascular Endothelial Cell ◽  
Expression Level ◽  
Vascular Endothelial ◽  
Microarray Datasets

Gravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized that it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells (HUVEC) to simulated microgravity (SMG) using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin (PG) transporter gene SLCO2A1 decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level of SLCO2A1, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.

scholarly journals Physiological concentrations of dietary polyphenols regulate vascular endothelial cell expression of genes important in cardiovascular health

2009 ◽  
Vol 103 (10) ◽  
pp. 1398-1403 ◽  
Author(s):  
Sonja K. Nicholson ◽  
Gregory A. Tucker ◽  
John M. Brameld
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
Cardiovascular Health ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Potential Health ◽  
Dietary Polyphenols ◽  
Expression Of Genes

Previous cell culture-based studies have shown potential health beneficial effects on gene expression of dietary polyphenols, including those found in red wine and green tea. However, these studies have tended to use higher concentrations (2–100 μm) than those observed in blood (0·1–1 μm) after consuming polyphenol-rich foods or beverages. The present study investigated effects of physiological concentrations of different classes of dietary polyphenol on the expression of genes important in cardiovascular health (endothelial NO synthase (eNOS), endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF)) by cultured vascular endothelial cells (human umbilical vein endothelial cells) in the absence or presence of H2O2. Resveratrol and quercetin (0·1–1 μm) increased eNOS and VEGF mRNA expression particularly in the absence of H2O2 (50 μm) and decreased H2O2-induced ET-1 mRNA expression (P < 0·001 for polyphenol × H2O2 interactions). Similarly, resveratrol and quercetin decreased endothelin secretion into the media, blocking the stimulatory effect of 50 μm-H2O2 (P < 0·001 for polyphenol × H2O2 interaction). Of the nine other polyphenols tested, only epigallocatechin gallate had similar effects on both the eNOS and ET-1 mRNA expression, but to a lesser extent than resveratrol at an equimolar concentration (0·1 μm). The observed effects on gene expression would be expected to result in vasodilation and thereby reduced blood pressure. Since only three of the eleven polyphenols tested had biological activity, it is unclear whether particular structures are important or whether the effects might relate to the relatively high antioxidant capacities of the three active polyphenols.

scholarly journals Effects of dietary polyphenols on gene expression in human vascular endothelial cells

2008 ◽  
Vol 67 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Sonja K. Nicholson ◽  
Gregory A. Tucker ◽  
John M. Brameld
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Ferulic Acid ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Physiological Concentration ◽  
Dietary Polyphenols

Previous studies have shown that consumption of fruit and vegetables plays a role in preventing the onset of CVD. These beneficial effects have been linked to the presence of polyphenolic compounds in plant-derived foods and their antioxidant capacity. It has been hypothesised that polyphenols may also have a direct effect on vascular endothelial cell growth and the expression of genes involved in angiogenesis and other roles of the endothelium. Previous studies in this area have tended to use concentrations of polyphenols that are supraphysiological (1–100 μm). The effects of more physiological concentrations (0·1 μm) of various individual polyphenols on gene expression were therefore investigated in cultured human umbilical vein endothelial cells (HUVEC) using both microarray and quantitative RT–PCR methodologies. Treatment of HUVEC with ferulic acid, quercetin or resveratrol (0·1 μm) resulted in changes to gene expression that for the three treatments amounted to significant (>2-fold) down-regulation of the expression of 363 genes and significant (>2-fold) up-regulation of 233 genes of the 10 000 genes present on the microarray. The majority of these genes were affected by resveratrol. Quantitative RT–PCR studies indicated that resveratrol (0·1 μm) significantly increased the expression of the gene encoding endothelial NO synthase (eNOS), which synthesises the vasodilator molecule NO, and both resveratrol and quercetin decreased expression of the potent vasoconstrictor, endothelin-1 (ET-1), while ferulic acid had no effect. The effects of resveratrol (0·1 μm) were also investigated when HUVEC were under oxidative stress following treatment with H2O2 (0–50 μm), which dose-dependently increased expression of eNOS and ET-1. Resveratrol stimulated eNOS mRNA in the absence of H2O2 and still allowed the increase with H2O2, but the effects were not additive. In contrast, resveratrol blocked the stimulatory effect of H2O2 on ET-1 expression. Hence, resveratrol has potent effects at a physiological concentration (0·1 μm) that would be expected to result in vasodilation and therefore help reduce blood pressure and the risk of CVD.

scholarly journals Formal meta-analysis of hypoxic gene expression profiles reveals a universal gene signature and cell type-specific effects

2021 ◽  
Author(s):  
Laura Puente-Santamaria ◽  
Lucia Sanchez-Gonzalez ◽  
Barbara Pilar Gonzalez-Serrano ◽  
Nuria Pescador ◽  
Oscar Hernan Martinez-Costa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Gene Expression Pattern ◽  
Cell Types ◽  
Gene Signature ◽  
Cell Type ◽  
Transcriptomic Response ◽  
Cell Type Specific

Background: Integrating transcriptional profiles results in the identification of gene expression signatures that are more robust than those obtained for individual datasets. However, direct comparison of datasets derived from heterogeneous experimental conditions is not possible and their integration requires the application of specific meta-analysis techniques. The transcriptional response to hypoxia has been the focus of intense research due to its central role in tissue homeostasis and in prevalent diseases. Accordingly, a large number of studies have determined the gene expression profile of hypoxic cells. Yet, in spite of this wealth of information, little effort have been done to integrate these dataset to produce a robust hypoxic signature. Results: We applied a formal meta-analysis procedure to a dataset comprising 425 RNAseq samples derived from 42 individual studies including 33 different cell types, to derive a pooled estimate of the effect of hypoxia on gene expression. This approach revealed that a large proportion of the transcriptome (8556 genes out of 20888) is significantly regulated by hypoxia. However, only a small fraction of the differentially expressed genes (1265 genes, 15%) show an effect size that, according to comparisons to gene pathways known to be regulated by hypoxia, is likely to be biologically relevant. By focusing on genes ubiquitously expressed we identified a signature of 291 genes robustly and consistently regulated by hypoxia. Finally, by a applying a moderator analysis we found that endothelial cells show a characteristic gene expression pattern that is significantly different from other cell types. Conclusion: By the application of a formal meta-analysis to hypoxic gene profiles, we have developed a robust gene signature that characterizes the transcriptomic response to low oxygen. In addition to identifying a universal set of hypoxia-responsive genes, we found a set of genes whose regulation is cell-type specific and suggest a unique metabolic response of endothelial cells to reduced oxygen tension.

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

scholarly journals Orai–vascular endothelial-cadherin signaling complex regulates high-glucose exposure-induced increased permeability of mouse aortic endothelial cells

2021 ◽  
Vol 9 (1) ◽  
pp. e002085
Author(s):  
Yuan Wei ◽  
Suwen Bai ◽  
YanHeng Yao ◽  
Wenxuan Hou ◽  
Junwei Zhu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Membrane ◽  
High Glucose ◽  
Expression Level ◽  
Vascular Endothelial ◽  
Aortic Endothelial Cells ◽  
Downstream Signaling ◽  
Signaling Complex ◽  
Aortic Endothelium ◽  
Aortic Endothelial

IntroductionDiabetes-associated endothelial barrier function impairment might be linked to disturbances in Ca2+ homeostasis. To study the role and molecular mechanism of Orais–vascular endothelial (VE)-cadherin signaling complex and its downstream signaling pathway in diabetic endothelial injury using mouse aortic endothelial cells (MAECs).Research design and methodsThe activity of store-operated Ca2+ entry (SOCE) was detected by calcium imaging after 7 days of high-glucose (HG) or normal-glucose (NG) exposure, the expression levels of Orais after HG treatment was detected by western blot analysis. The effect of HG exposure on the expression of phosphorylated (p)-VE-cadherin and VE-cadherin on cell membrane was observed by immunofluorescence assay. HG-induced transendothelial electrical resistance was examined in vitro after MAECs were cultured in HG medium. FD-20 permeability was tested in monolayer aortic endothelial cells through transwell permeability assay. The interactions between Orais and VE-cadherin were detected by co-immunoprecipitation and immunofluorescence technologies. Immunohistochemical experiment was used to detect the expression changes of Orais, VE-cadherin and p-VE-cadherin in aortic endothelium of mice with diabetes.Results(1) The expression levels of Orais and activity of SOCE were significantly increased in MAECs cultured in HG for 7 days. (2) In MAECs cultured in HG for 7 days, the ratio of p-VE-cadherin to VE-cadherin expressed on the cell membrane and the FD-20 permeability in monolayer endothelial cells increased, indicating that intercellular permeability increased. (3) Orais and VE-cadherin can interact and enhance the interaction ratio through HG stimulation. (4) In MAECs cultured with HG, the SOCE activator ATP enhanced the expression level of p-VE-cadherin, and the SOCE inhibitor BTP2 decreased the expression level of p-VE-cadherin. (5) Significantly increased expression of p-VE-cadherin and Orais in the aortic endothelium of mice with diabetes.ConclusionHG exposure stimulated increased expression of Orais in endothelial cells, and increased VE-cadherin phosphorylation through Orais–VE-cadherin complex and a series of downstream signaling pathways, resulting in disruption of endothelial cell junctions and initiation of atherosclerosis.

scholarly journals Verticillium wilt resistant and susceptible olive cultivars express a very different basal set of genes in roots

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jorge A. Ramírez-Tejero ◽  
Jaime Jiménez-Ruiz ◽  
Alicia Serrano ◽  
Angjelina Belaj ◽  
Lorenzo León ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Growth And Development ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Expression Level ◽  
Resistant Cultivars ◽  
Pathogen Invasion ◽  
Wide Range ◽  
Olive Cultivars

Abstract Background Olive orchards are threatened by a wide range of pathogens. Of these, Verticillium dahliae has been in the spotlight for its high incidence, the difficulty to control it and the few cultivars that has increased tolerance to the pathogen. Disease resistance not only depends on detection of pathogen invasion and induction of responses by the plant, but also on barriers to avoid the invasion and active resistance mechanisms constitutively expressed in the absence of the pathogen. In a previous work we found that two healthy non-infected plants from cultivars that differ in V. dahliae resistance such as ‘Frantoio’ (resistant) and ‘Picual’ (susceptible) had a different root morphology and gene expression pattern. In this work, we have addressed the issue of basal differences in the roots between Resistant and Susceptible cultivars. Results The gene expression pattern of roots from 29 olive cultivars with different degree of resistance/susceptibility to V. dahliae was analyzed by RNA-Seq. However, only the Highly Resistant and Extremely Susceptible cultivars showed significant differences in gene expression among various groups of cultivars. A set of 421 genes showing an inverse differential expression level between the Highly Resistant to Extremely Susceptible cultivars was found and analyzed. The main differences involved higher expression of a series of transcription factors and genes involved in processes of molecules importation to nucleus, plant defense genes and lower expression of root growth and development genes in Highly Resistant cultivars, while a reverse pattern in Moderately Susceptible and more pronounced in Extremely Susceptible cultivars were observed. Conclusion According to the different gene expression patterns, it seems that the roots of the Extremely Susceptible cultivars focus more on growth and development, while some other functions, such as defense against pathogens, have a higher expression level in roots of Highly Resistant cultivars. Therefore, it seems that there are constitutive differences in the roots between Resistant and Susceptible cultivars, and that susceptible roots seem to provide a more suitable environment for the pathogen than the resistant ones.

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