C/<scp>EBP</scp> transcription factors regulate <scp>NADPH</scp> oxidase in human aortic smooth muscle cells

Manea, Simona-Adriana; Todirita, Andra; Raicu, Monica; Manea, Adrian

doi:10.1111/jcmm.12289

Cited by 39 publications

(31 citation statements)

References 46 publications

(60 reference statements)

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“…ROS can also impair telomerase activity, with telomere attrition being a predictive marker for cardiovascular dysfunction, metabolic syndrome and other age- and DOHaD-related pathologies (Hallows, et al 2012). It is therefore possible that an in increase in ROS levels is the initial stimulus that reprograms the ART embryo, which employs transcription factors like NFE2L2, CEBPs (Manea, et al 2014), and p53 to exert acute transcriptional responses and subsequent chromatin remodeling that persists throughout development, leading to different cell type-contextual expression patterns.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Feuer¹,

Liu²,

Donjacour³

et al. 2017

Reproduction

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Stressful environmental exposures incurred early in development can affect postnatal metabolic health and susceptibility to non-communicable diseases in adulthood, although the molecular mechanisms by which this occurs have yet to be elucidated. Here we use a mouse model to investigate how assorted in vitro exposures restricted exclusively to the preimplantation period affect transcription both acutely in embryos and long-term in subsequent offspring adult tissues, to determine if reliable transcriptional markers of in vitro stress are present at specific developmental time points and throughout development. Each in vitro fertilization or embryo culture environment led to a specific and unique blastocyst transcriptional profile, but we identified a common 18-gene and 9-pathway signature of preimplantation embryo manipulation that was present in all in vitro embryos irrespective of culture condition or method of fertilization. This fingerprint did not persist throughout development and there was no clear transcriptional cohesion between adult IVF offspring tissues or compared to their preceding embryos, indicating a tissue-specific impact of in vitro stress on gene expression. However, the transcriptional changes present in each IVF tissue were targeted by the same upstream transcriptional regulators, which provide insight as to how acute transcriptional responses to stressful environmental exposures might be preserved throughout development to influence adult gene expression.

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Section: Discussionmentioning

confidence: 99%

Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Feuer¹,

Liu²,

Donjacour³

et al. 2017

Reproduction

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“…IFN‐γ induces ICAM‐1 mRNA expression in smooth muscle cells (Chung et al , ). IFN‐γ also has a strong impact on superoxide production by up‐regulation of the expression and activity of NOXs in human aortic smooth muscle cells (Manea et al , ).…”

Section: Mechanisms Linking Pvat Inflammation To Vascular Dysfunctionmentioning

confidence: 99%

Perivascular adipose tissue inflammation in vascular disease

Nosalski

Guzik

2017

British J Pharmacology

287

237

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Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vasoprotective adipocyte-derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6 and TNF-α) and chemokines [RANTES (CCL5) and MCP-1 (CCL2)]. These adipocyte-derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN-γ or IL-17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue.

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“…NOX5δ, NOX5ε and Noxζ do not seem to produce appreciable amounts of O 2 − , and their functional significance is unclear. Epigenetic factors, including overexpression of histone deacetylase 2, cause upregulation of the NOX5 gene promotor activity in vascular smooth muscle cells (Manea, Todirita, Raicu, & Manea, ).…”

Section: Regulation Of Nox5mentioning

confidence: 99%

NOX5: Molecular biology and pathophysiology

Touyz

Anagnostopoulou

Ríos

et al. 2019

Experimental Physiology

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New Findings What is the topic of this review? This review provides a comprehensive overview of Nox5 from basic biology to human disease and highlights unique features of this Nox isoform What advances does it highlight? Major advances in Nox5 biology relate to crystallization of the molecule and new insights into the pathophysiological role of Nox5. Recent discoveries have unravelled the crystal structure of Nox5, the first Nox isoform to be crystalized. This provides new opportunities to develop drugs or small molecules targeted to Nox5 in an isoform‐specific manner, possibly for therapeutic use. Moreover genome wide association studies (GWAS) identified Nox5 as a new blood pressure‐associated gene and studies in mice expressing human Nox5 in a cell‐specific manner have provided new information about the (patho) physiological role of Nox5 in the cardiovascular system and kidneys. Nox5 seems to be important in the regulation of vascular contraction and kidney function. In cardiovascular disease and diabetic nephropathy, Nox5 activity is increased and this is associated with increased production of reactive oxygen species and oxidative stress implicated in tissue damage. Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), comprise seven family members (Nox1–Nox5 and dual oxidase 1 and 2) and are major producers of reactive oxygen species in mammalian cells. Reactive oxygen species are crucially involved in cell signalling and function. All Noxs share structural homology comprising six transmembrane domains with two haem‐binding regions and an NADPH‐binding region on the intracellular C‐terminus, whereas their regulatory systems, mechanisms of activation and tissue distribution differ. This explains the diverse function of Noxs. Of the Noxs, NOX5 is unique in that rodents lack the gene, it is regulated by Ca 2+ , it does not require NADPH oxidase subunits for its activation, and it is not glycosylated. NOX5 localizes in the perinuclear and endoplasmic reticulum regions of cells and traffics to the cell membrane upon activation. It is tightly regulated through numerous post‐translational modifications and is activated by vasoactive agents, growth factors and pro‐inflammatory cytokines. The exact pathophysiological significance of NOX5 remains unclear, but it seems to be important in the physiological regulation of sperm motility, vascular contraction and lymphocyte differentiation, and NOX5 hyperactivation has been implicated in cardiovascular disease, kidney injury and cancer. The field of NOX5 biology is still in its infancy, but with new insights into its biochemistry and cellular regulation, discovery of the NOX5 crystal structure and genome‐wide association studies implicating NOX5 in disease, the time is now ripe to advance NOX5 research. This review provides a comprehensive overview of our current understanding of NOX5, from basic ...

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C/EBP transcription factors regulate NADPH oxidase in human aortic smooth muscle cells

Cited by 39 publications

References 46 publications

Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

Perivascular adipose tissue inflammation in vascular disease

NOX5: Molecular biology and pathophysiology

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