NADPH oxidase 4 and its role in the cardiovascular system

Gray, Sara; Shah, Ajay; Smyrnias, Ioannis

doi:10.1530/vb-19-0014

Cited by 26 publications

(16 citation statements)

References 63 publications

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“…NADPH oxidase 4(NOX 4) is a dual heme-containing enzyme that spans the membrane 6 times and produces reactive oxygen species, namely hydrogen peroxide ( Gray et al, 2019 ). NOX4 is mainly related to cell growth, apoptosis, differentiation, ECM synthesis and secretion.…”

Section: Discussionmentioning

confidence: 99%

Keloid Biomarkers and Their Correlation With Immune Infiltration

Yin

Bu²,

Fang³

et al. 2022

Front. Genet.

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Objective: This work aimed to verify the candidate biomarkers for keloid disorder (KD), and analyze the role of immune cell infiltration (ICI) in the pathology of keloid disorder.Methods: The keloid-related datasets (GSE44270 and GSE145725) were retrieved from the Gene Expression Omnibus (GEO). Then, differential expressed genes (DEGs) were identified by using the “limma” R package. Support vector machine-recursive feature elimination (SVM-RFE) and LASSO logistic regression were utilized for screening candidate biomarkers of KD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of candidate biomarkers. The candidate biomarkers were further verified through qRT-PCR of keloid lesions and the matched healthy skin tissue collected from eight cases. In addition, ICI in keloid lesions was estimated through single-sample gene-set enrichment analysis (ssGSEA). Finally, the potential drugs to the treatment of KD were predicted in the Connectivity Map Database (CMAP).Results: A total of 406 DEGs were identified between keloid lesion and healthy skin samples. Among them, STC2 (AUC = 0.919), SDC4 (AUC = 0.970), DAAM1 (AUC = 0.966), and NOX4 (AUC = 0.949) were identified as potential biomarkers through the SVM-RFE, LASSO analysis and ROC analysis. The differential expressions of SDC4, DAAM1, and NOX4 were further verified in collected eight samples by qRT-PCR experiment. ICI analysis result showed a positive correlation of DAAM1 expression with monocytes and mast cells, SDC4 with effector memory CD4+ T cells, STC2 with T follicular helper cells, and NOX4 with central memory CD8+ T cells. Finally, a total of 13 candidate small molecule drugs were predicted for keloids treatment in CMAP drug database.Conclusion: We identified four genes that may serve as potential biomarkers for KD development and revealed that ICI might play a critical role in the pathogenesis of KD.

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Section: Discussionmentioning

confidence: 99%

Keloid Biomarkers and Their Correlation With Immune Infiltration

Yin

Bu²,

Fang³

et al. 2022

Front. Genet.

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“…The Nox family is comprised of Nox 1, Nox 2, Nox 3, Nox 4, Nox 5, dual oxidase 1 (Duox 1), and Duox 2 which in states of hyperactivity produce excessive levels of ROS, contributing to endothelial dysfunction, inflammation, and cardiovascular remodeling. Angiotensin II regulates Nox function in vessels [ 51 , 52 , 53 , 54 ]. Mice and rats treated with this peptide hormone expressed increased generation of ROS and enhanced activity of Nox 1, Nox 2, and Nox 4 [ 21 ].…”

Section: Oxidative Stress In Hypertensionmentioning

confidence: 99%

Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives

et al. 2022

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Arterial hypertension (HTN) is one of the most prevalent entities globally, characterized by increased incidence and heterogeneous pathophysiology. Among possible etiologies, oxidative stress (OS) is currently extensively studied, with emerging evidence showing its involvement in endothelial dysfunction and in different cardiovascular diseases (CVD) such as HTN, as well as its potential as a therapeutic target. While there is a clear physiological equilibrium between reactive oxygen species (ROS) and antioxidants essential for many cellular functions, excessive levels of ROS lead to vascular cell impairment with decreased nitric oxide (NO) availability and vasoconstriction, which promotes HTN. On the other hand, transcription factors such as nuclear factor erythroid factor 2-related factor 2 (Nrf2) mediate antioxidant response pathways and maintain cellular reduction–oxidation homeostasis, exerting protective effects. In this review, we describe the relationship between OS and hypertension-induced endothelial dysfunction and the involvement and therapeutic potential of Nrf2 in HTN.

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“… Sequence of events illustrating interactions between NADPH oxidases, mitochondria, (endothelial) NOS and their products in vascular health and disease. While excess ROS produced from NADPH oxidases contributes to pathology, note that increased activation of some NOX isoforms, such as NOX4, may serve a cardioprotective function [ 64 ]. Examples of NOX inhibitors include GKT137831, Setanaxib, and apocynin.…”

Section: Figurementioning

confidence: 99%

Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical Studies

et al. 2022

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Reactive oxygen species (ROS) can be beneficial or harmful in health and disease. While low levels of ROS serve as signaling molecules to regulate vascular tone and the growth and proliferation of endothelial cells, elevated levels of ROS contribute to numerous pathologies, such as endothelial dysfunctions, colon cancer, and fibrosis. ROS and their cellular sources have been extensively studied as potential targets for clinical intervention. Whereas various ROS sources are important for different pathologies, four NADPH oxidases (NOX1, NOX2, NOX4, and NOX5) play a prominent role in homeostasis and disease. NOX1-generated ROS have been implicated in hypertension, suggesting that inhibition of NOX1 may be a promising therapeutic approach. NOX2 and NOX4 oxidases are of specific interest due to their role in producing extra- and intracellular hydrogen peroxide (H2O2). NOX4-released hydrogen peroxide activates NOX2, which in turn stimulates the release of mitochondrial ROS resulting in ROS-induced ROS release (RIRR) signaling. Increased ROS production from NOX5 contributes to atherosclerosis. This review aims to summarize recent findings on NOX enzymes and clinical trials inhibiting NADPH oxidases to target pathologies including diabetes, idiopathic pulmonary fibrosis (IPF), and primary biliary cholangitis (PBC).

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NADPH oxidase 4 and its role in the cardiovascular system

Cited by 26 publications

References 63 publications

Keloid Biomarkers and Their Correlation With Immune Infiltration

Keloid Biomarkers and Their Correlation With Immune Infiltration

Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives

Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical Studies

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