Identification of Key Non-coding RNAs and Transcription Factors in Calcific Aortic Valve Disease

Guo, Shuai; Zhang, Erli; Zhang, Bin; Liu, Qingrong; Meng, Zhen; Li, Ziang; Wang, Can; Gong, Zhaoting; Wu, Yongjian

doi:10.3389/fcvm.2022.826744

Cited by 4 publications

(4 citation statements)

References 78 publications

(84 reference statements)

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“…Another research reported that GZMB mediates IL-8/macrophage inflammatory protein-2 secretion ( 39 ). Further, Guo et al’s study also reported that GZMB was differentially expressed gene in CAVD datasets ( 40 ), which supports our analysis.…”

Section: Discussionsupporting

confidence: 89%

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease

Qin

Chen²,

Li³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundCAVD is a common cardiovascular disease, but currently there is no drug treatment. Therefore, it is urgent to find new and effective drug therapeutic targets. Recent evidence has shown that the infiltration of M1 macrophages increased in the calcified aortic valve tissues, but the mechanism has not been fully elucidated. The purpose of this study was to explore the shared gene characteristics and molecular mechanisms of macrophages M1 polarization in CAVD, in order to provide a theoretical basis for new drugs of CAVD.MethodsThe mRNA datasets of CAVD and M1 polarization were downloaded from Gene Expression Omnibus (GEO) database. R language, String, and Cytoscape were used to analyze the functions and pathways of DEGs and feature genes. Immunohistochemical staining and Western Blot were performed to verify the selected hub genes.ResultsCCR7 and GZMB were two genes appeared together in hub genes of M1-polarized and CAVD datasets that might be involved in the process of CAVD and macrophages M1 polarization. CCR7 and CD86 were significantly increased, while CD163 was significantly decreased in the calcified aortic valve tissues. The infiltration of M1 macrophages was increased, on the contrary, the infiltration of M2 macrophages was decreased in the calcified aortic valve tissues.ConclusionThis study reveals the shared gene characteristics and molecular mechanisms of CAVD and macrophages M1 polarization. The hub genes and pathways we found may provide new ideas for the mechanisms underlying the occurrence of M1 polarization during CAVD process.

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Section: Discussionsupporting

confidence: 89%

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease

Qin

Chen²,

Li³

et al. 2023

Front. Cardiovasc. Med.

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“…According to Okazaki and Honjo (2007) , Gotsman et al (2007) , Weyand et al (2018) , and Sun et al (2020) , Bu et al (2011) alterations in PD-1 or PD-L1 expression can influence the degree of inflammation and condition of coronary plaques in atherosclerosis. Granzyme B ( GZMB ) is a protease secreted by T cells and NK cells and is known for its pro-apoptotic properties ( Voskoboinik et al, 2015 ; Guo et al, 2022 ). Previous by qPCR and immunohistochemistry data confirmed that GZMB expression was higher in calcified aortic valve tissues than in control valves ( Ohukainen et al, 2015 ; Guo et al, 2022 ), which is in line with our results, where we found correlations between GZMB expression and calcification grade in coronary and tibial artery.…”

Section: Discussionmentioning

confidence: 99%

“…Granzyme B ( GZMB ) is a protease secreted by T cells and NK cells and is known for its pro-apoptotic properties ( Voskoboinik et al, 2015 ; Guo et al, 2022 ). Previous by qPCR and immunohistochemistry data confirmed that GZMB expression was higher in calcified aortic valve tissues than in control valves ( Ohukainen et al, 2015 ; Guo et al, 2022 ), which is in line with our results, where we found correlations between GZMB expression and calcification grade in coronary and tibial artery. Furthermore, we have not found signs of adaptive immune response deregulation in the blood of the subject with vascular calcification.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of calcified soft tissues revealed shared deregulated pathways

Ibragimova,

Stanishevskiy,

Plakkhin

et al. 2023

Front. Aging Neurosci.

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IntroductionCalcification of soft tissues is a common age-related pathology that primarily occurs within vascular tissue. The mechanisms underlying pathological calcification in humans and tissue specificity of the process is still poorly understood. Previous studies examined calcified tissues on one to one basis, thus preventing comparison of deregulated pathways across tissues.PurposeThis study aimed to establish common and tissue-specific changes associated with calcification in aorta, artery tibial, coronary artery and pituitary gland in subjects from the Genotype-Tissue Expression (GTEx) dataset using its RNA sequencing and histological data.MethodsWe used publicly available data from the GTEx database https://gtexportal.org/home/aboutGTEx. All GTEx tissue samples were derived by the GTEx consorcium from deceased donors, with age from 20 to 79, both men and women. GTEx study authorization was obtained via next-of-kin consent for the collection and banking of de-identified tissue samples for scientific research. Hematoxylin and eosin (H&E) staining of arteries were manually graded based on the presence of calcification on a scale from zero to four, where zero designates absence of calcification and four designates severe calcification. Samples with fat contamination and mislabeled tissues were excluded, which left 430 aorta, 595 artery tibial, 124 coronary artery, and 283 pituitary samples for downstream gene expression analysis. Transcript levels of protein-coding genes were associated with calcification grade using sex, age bracket and cause of death as covariates, and tested for pathway enrichment using gene set enrichment analysis.ResultsWe identified calcification deposits in 28 (6.5%) aortas, 121 (20%), artery tibials, 54 (43%), coronary arteries, and 24 (8%) pituitary glands of GTEx subjects. We observed an age-dependent increase in incidence of calcification in all vascular tissues, but not in pituitary. Subjects with calcification in the artery tibial were significantly more likely to have calcification in the coronary artery (OR = 2.56, p = 6.3e-07). Markers of calcification previously established in preclinical and in vitro studies, e.g., BMP2 and RUNX2, were deregulated in the calcified tibial and coronary arteries, confirming the relevance of these genes to human pathology. Differentially expressed genes associated with calcification poorly overlapped across tissues suggesting tissue-specific nuances in mechanisms of calcification. Nevertheless, calcified arteries unanimously down-regulated pathways of intracellular transport and up-regulated inflammatory pathways suggesting these as universal targets for pathological calcification. In particular, PD-1 and PD-L1 genes were up-regulated in calcified tissues but not in the blood of the same subjects, suggesting that localized inflammation contributes to pathological calcification.ConclusionPathological calcification is a prevalent disease of aging that shares little changes in expression in individual genes across tissues. However, our analysis suggests that it potentially can be targeted by alleviating local inflammation of soft tissues.

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“…Presently, operative resection, chemotherapy, targeted-therapies, and immunotherapies dominate the treatment of CRC ( 27 , 28 ). The selection of therapeutic strategies is determined by each patient’s medical status and the clinical characteristics and phase of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Screening of key genes related to ferroptosis and a molecular interaction network analysis in colorectal cancer using machine learning and bioinformatics

Feng¹,

Jiang²,

Kou³

2023

J Gastrointest Oncol

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Background This study sought to identify the key genes and molecular interactions related to ferroptosis in colorectal cancer (CRC) using machine-learning and bioinformatics analyses. Methods The Gene Expression Omnibus (National Institutes of Health, US) datasets for CRC were downloaded from the National Center for Biotechnology Information (NCBI) ( https://www.ncbi.nlm.nih.gov/ ). The 291 ferroptosis genes were downloaded and screened from the FerrDb ( http://www.zhounan.org/ferrdb ) and GeneCards ( https://www.genecards.org/ ) databases. The least absolute shrinkage and selection operator regression model and support vector machine model were constructed to identify the different ferroptosis-related hub genes. The immune infiltrates were identified and a survival curve analysis was conducted. Results We identified 11 ferroptosis-related differentially expressed genes (DEGs) from the COADREAD (Colon and Rectal Cancer) dataset. We found that angiopoietin-related protein 7 ( ANGPTL7 ) gene expression was positively correlated to both the neuroglobin ( NGB ) (r=0.678) and ceruloplasmin (CP) (r=0.454) genes but was negatively correlated with transferrin receptor 2 ( TFR2 ) expression (r=–0.426). In addition, TFR2 gene expression was positively correlated with the arachidonate lipoxygenase 3 ( ALOXE3 ) (r=0.452) and carbonic anhydrase 9 ( CA9 ) (r=0.411) genes. A total of 4 hub genes were identified by the machine-learning analysis [i.e., NADPH oxidase 4 ( NOX4 ), TFR2, ALOXE3 , and CA9 ]. The expression of the NOX4 gene was significantly positively correlated with neutrophil (r=0.543) and M0 macrophage (r=0.422) infiltration. In addition, a positive correlation between ALOXE3 and activated natural-killer cells (r=0.356) was found. Conversely, the NOX4, TFR2 , and CA9 genes were negatively correlated with the resting mast cells. A strong negative correlation was observed between NOX4 and CD160 antigen ( CD160 ) expression; however, a significant positive correlation was observed between NOX4 and transforming growth factor beta receptor 1 ( TGFBR1 ) expression (r=0.397). The patients had a more favorable prognosis when the NOX4 expression levels were relatively low. Conclusions Our study identified 4 ferroptosis-related DEGs in CRC (i.e., NOX4, TFR2 , ALOXE3 , and CA9 ), and fur...

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Identification of Key Non-coding RNAs and Transcription Factors in Calcific Aortic Valve Disease

Cited by 4 publications

References 78 publications

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease

Comparative analysis of calcified soft tissues revealed shared deregulated pathways

Screening of key genes related to ferroptosis and a molecular interaction network analysis in colorectal cancer using machine learning and bioinformatics

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