Abstract:
SIGNIFICANCE:Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction. RECENT ADVANCES:While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms-proteins, sugars, and membrane structures-at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-β signaling and Wnt/β-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD. CRITICAL ISSUES:While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease. FUTURE DIRECTIONS:Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401-414.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Fernández Esmerats J,Heath J,Jo Hdoi
10.1089/ars.2015.6554subject
Has Abstractpub_date
2016-09-01 00:00:00pages
401-14issue
7eissn
1523-0864issn
1557-7716journal_volume
25pub_type
杂志文章,评审abstract:AIMS:Cystathionine β-synthase (CBS) catalyzes the first and rate-limiting step in the two-step trans-sulfuration pathway that converts homocysteine to cysteine. It is also one of three major enzymes responsible for the biogenesis of H2S, a signaling molecule. We have previously demonstrated that CBS is activated in cel...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2014.5891
更新日期:2015-02-10 00:00:00
abstract:: Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is als...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8124
更新日期:2021-02-20 00:00:00
abstract:AIMS:Oxidative stress is thought to be involved in Friedreich's ataxia (FRDA), yet it has not been demonstrated in the target neurons that are first to degenerate. Using the YG8R mouse model of FRDA, microarray and neuritic growth experiments were carried out in the dorsal root ganglion (DRG), the primary site of neuro...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4537
更新日期:2013-11-01 00:00:00
abstract:AIMS:Protein S-glutathionylation, the formation of a mixed disulfide between glutathione and protein thiols, is an oxidative modification that has emerged as a new signaling paradigm, potentially linking oxidative stress to chronic inflammation associated with heart disease, diabetes, cancer, lung disease, and aging. U...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6531
更新日期:2016-11-20 00:00:00
abstract:: Significance: Streptococcus pneumoniae (Spn), a facultative anaerobic Gram-positive human pathogen with increasing rates of penicillin and macrolide resistance, is a major cause of lower respiratory tract infections worldwide. Pneumococci are a primary agent of severe pneum...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7964
更新日期:2020-08-14 00:00:00
abstract:SIGNIFICANCE:MicroRNAs (miRNAs) are important regulators of gene expression and define part of the epigenetic signature. Their influence on every realm of biomedicine is established and progressively increasing. The impact of environment on human health is enormous. Among environmental risk factors impinging on quality...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7175
更新日期:2018-03-20 00:00:00
abstract::To study early subcellular pathologic changes of tumorigenesis in mouse skin and possible modulation by overexpression of the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD), skin keratinocytes from nontransgenic (Ntg) and transgenic (TgH) mice overexpressing MnSOD topically treated with one do...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308604773934297
更新日期:2004-06-01 00:00:00
abstract::A model has been developed for the hemopexin receptor-mediated heme transport system based on iron uptake in yeast. Two steps are required: reduction followed by oxidation by a multi-copper-oxidase. Furthermore, in the hemopexin system, the surface redox events have been linked with gene regulation. The impermeable Cu...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.4-753
更新日期:2000-01-01 00:00:00
abstract:: Significance: Atherosclerotic cardiovascular diseases (ACVDs) continue to be a primary cause of mortality worldwide in adults aged 35-70 years, occurring more often in countries with lower economic development, and they constitute an ever-growing global burden that has a c...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7955
更新日期:2021-01-01 00:00:00
abstract::In this study, we sought to investigate the putative association of the oxidized metabolites derived from linoleic acid (OXFAs) with pediatric nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). We studied 80 obese adolescents (age 13.3 ± 3.31 years; body mass index 33.0 ± 6.79 kg/m(2)), who underwent ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5466
更新日期:2014-01-10 00:00:00
abstract:SIGNIFICANCE:Understanding isoform- and context-specific subcellular Nox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase compartmentalization allows relevant functional inferences. This review addresses the interplay between Nox NADPH oxidases and the endoplasmic reticulum (ER), an increasingly evid...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5605
更新日期:2014-06-10 00:00:00
abstract::Diabetes mellitus is a multifactorial disease, classically influenced by genetic determinants of individual susceptibility and by environmental accelerating factors, such as lifestyle. It is considered a major health concern,as its incidence is increasing at an alarming rate, and the high invalidating effects of its l...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2484
更新日期:2009-12-01 00:00:00
abstract:AIMS:Heart failure (HF) is characterized by regionalized contractile alterations resulting in loss of the transmural contractile gradient across the left ventricular free wall. We tested whether a regional alteration in mitochondrial oxidative metabolism during HF could affect myofilament function through protein kinas...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4534
更新日期:2013-03-20 00:00:00
abstract:AIMS:Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its solubl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6343
更新日期:2016-03-01 00:00:00
abstract::The superoxide-generating NADPH oxidase NOX1 is thought to be involved in signaling by the angiotensin II-receptor AT1R. However, underlying signaling steps are poorly understood. In this study, we investigated the effect of AngII on aortic smooth muscle from wild-type and NOX1-deficient mice. NOX1-deficient cells sho...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2584
更新日期:2009-10-01 00:00:00
abstract::Nuclear factor, erythroid 2 related factor 2 (Nrf2) belongs to the Cap'n'collar/basic region leucine zipper (CNC-bZIP) transcription factor family, and is activated by diverse oxidants, pro-oxidants, antioxidants, and chemopreventive agents. After phosphorylation and dissociation from the cytoplasmic inhibitor, Kelch-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.76
更新日期:2006-01-01 00:00:00
abstract:SIGNIFICANCE:Oxidative stress and damage are well-established components of neurodegenerative diseases, contributing to neuronal death during disease progression. Here, we consider key K(+) channels as target proteins that can undergo oxidative modulation, describe what is understood about how this influences disease p...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6007
更新日期:2015-02-20 00:00:00
abstract:SIGNIFICANCE:Calcium (Ca2+) hypothesis of Alzheimer's disease (AD) gains popularity. It points to new signaling pathways that may underlie AD pathogenesis. Based on calcium hypothesis, novel targets for the development of potential AD therapies are identified. Recent Advances: Recently, the key role of neuronal store-o...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2018.7506
更新日期:2018-10-20 00:00:00
abstract:AIMS:Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases involved in oxidant defense and signal transduction. Despite much study, the precise roles of conserved residues remain poorly defined. In this study, we carried out extensive functional and structural characterization of 10 variants of such residues ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6922
更新日期:2018-03-01 00:00:00
abstract:SIGNIFICANCE:The discovery of the oxidoreductase disulfide bond protein A (DsbA) in 1991 opened the way to the unraveling of the pathways of disulfide bond formation in the periplasm of Escherichia coli and other Gram-negative bacteria. Correct oxidative protein folding in the E. coli envelope depends on both the DsbA/...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4864
更新日期:2013-07-01 00:00:00
abstract:SIGNIFICANCE:Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS i...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5785
更新日期:2014-11-01 00:00:00
abstract:: Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including we...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8059
更新日期:2021-01-10 00:00:00
abstract:: Aims: Nuclear factor (erythroid-derived 2)-like-2 factor (NRF-2) is a transcription factor well known to provide an advantage for cancer growth and survival regulating the cellular redox pathway. In breast cancer cells, we recently identified the monomeric heme-globin neur...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7870
更新日期:2020-02-01 00:00:00
abstract::Anthracyclines are widely used in anticancer protocols, but can induce cardiotoxicity by mechanisms that mainly involve oxidative damage and mitochondrial dysfunction. Radiotherapy (RT) can also impair cardiac function by promoting myocardial fibrosis, microvascular damage, and decreased density of myocardial capillar...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7842
更新日期:2019-11-20 00:00:00
abstract:: Significance: T lymphocytes, as part of the adaptive immune system, possess the ability to activate and function in extreme cellular microenvironments, which requires these cells to remain highly malleable. One mechanism in which T lymphocytes achieve this adaptability is ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8042
更新日期:2020-04-30 00:00:00
abstract::Oxidative stress plays a significant role in the pathogenesis of coronary artery disease (CAD). A p22(phox)-based NAD(P)H oxidase acts as a potent superoxide-generating system in the vasculature. We studied the association of the A640G and the C242T polymorphisms with clinical risk factors, endothelial function, and s...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860260220184
更新日期:2002-08-01 00:00:00
abstract:: Aims: In this study, we investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in autoimmune diseases. We focus on oxidative regulation at the interaction between antigen-presenting cells (APCs) and T cells, and consequent effect of ROS a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7788
更新日期:2020-01-20 00:00:00
abstract:SIGNIFICANCE:Chronic myeloid leukemia (CML) involves the malignant transformation of hematopoietic stem cells, defined largely by the Philadelphia chromosome and expression of the breakpoint cluster region-Abelson (BCR-ABL) oncoprotein. Pharmacological tyrosine kinase inhibitors (TKIs), including imatinib mesylate, hav...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6096
更新日期:2015-06-01 00:00:00
abstract::Although the essential role of selenium for cellular immune responses is obvious, delineation of the functions is lacking because selenium can either promote or inhibit cell growth, cytokine production, and activation of transcription factor nuclear factor-kappaB (NF-kappaB). Studies with human thioredoxin-1 (Trx-1)-t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.9.115
更新日期:2007-01-01 00:00:00
abstract:AIMS:The purpose of this study was to investigate differential nicotinamide adenine dinucleotide phosphate, reduced (NADPH) production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines and whether these differences are predictive of sensitivity to the chemotherapeutic β...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2017.7048
更新日期:2018-10-01 00:00:00