NADPH oxidase: its potential role in promotion of pulmonary arterial hypertension

Peng, Junwen; Liu, Bin; Xu, Jinyun; Peng, Jun; Luo, Xiu-Ju

doi:10.1007/s00210-017-1359-2

Cited by 21 publications

(12 citation statements)

References 65 publications

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“…Studies from other labs and ours have repeatedly demonstrated that NOX-derived ROS contributes greatly to myocardial/cerebral ischemic injury [8][9][10], endothelial dysfunction [11,12], and vascular remodeling [13,14]. There is growing evidence that NOX is activated in animals or humans with PAH, indicating that NOX-derived ROS may contribute to the development of PAH [15][16][17]. Furthermore, our previous studies have demonstrated that NOX coordinates with vascular peroxidase 1 (VPO1) to amplify the role of NOX-derived ROS in mediation of oxidative injury in myocardial ischemia/reperfusion injury and vascular remodeling in PAH [6,18] because VPO1 can catalyze NOX-derived hydrogen peroxide (H 2 O 2 ) to produce more powerful oxidant hypochlorous acid (HOCl).…”

Section: Introductionmentioning

confidence: 86%

“…Although NOX inhibitors, such as apocynin and diphenyleneiodonium (DPI), showed therapeutic effects on PAH animals [17], they lacked clinical value due to the nonspecific effect and unacceptable toxicity. Actually, the efforts to seek ideal NOX inhibitors, particularly from Chinese traditional herbs, for prevention and therapy of PAH have never stopped.…”

Section: Introductionmentioning

confidence: 99%

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Magnesium Lithospermate B Derived from Salvia miltiorrhiza Ameliorates Right Ventricle Remodeling in Pulmonary Hypertensive Rats via Inhibition of NOX/VPO1 Pathway

Peng

Wang

et al. 2019

Planta Med

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Right ventricle (RV) remodeling is a major pathological feature in pulmonary arterial hypertension (PAH). Magnesium lithospermate B (MLB) is a compound isolated from the roots of Salvia miltiorrhiza and it possesses multiple pharmacological activities such as anti-inflammation and antioxidation. This study aims to investigate whether MLB is able to prevent RV remodeling in PAH and the underlying mechanisms. In vivo, SD rats were exposed to 10% O2 for 21 d to induce RV remodeling, which showed hypertrophic features (increases in the ratio of RV weight to tibia length, cellular size, and hypertrophic marker expression), accompanied by upregulation in expression of NADPH oxidases (NOX2 and NOX4) and vascular peroxidase 1 (VPO1), increases in hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) production and elevation in phosphorylation levels of ERK; these changes were attenuated by treating rats with MLB. In vitro, the cultured H9c2 cells were exposed to 3% O2 for 24 h to induce hypertrophy, which showed hypertrophic features (increases in cellular size and hypertrophic marker expression). Administration of MLB or VAS2870 (a positive control for NOX inhibitor) could prevent cardiomyocyte hypertrophy concomitant with decreases in NOX (NOX2 and NOX4) and VPO1 expression, H2O2 and HOCl production, and ERK phosphorylation. Based on these observations, we conclude that MLB is able to prevent RV remodeling in hypoxic PAH rats through a mechanism involving a suppression of NOX/VPO1 pathway as well as ERK signaling pathway. MLB may possess the potential clinical value for PAH therapy.

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Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Magnesium Lithospermate B Derived from Salvia miltiorrhiza Ameliorates Right Ventricle Remodeling in Pulmonary Hypertensive Rats via Inhibition of NOX/VPO1 Pathway

Peng

Wang

et al. 2019

Planta Med

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“…The contribution of Nox2 in PAH is supported by even a larger body of literature [87,93] and was shown to be involved in pulmonary artery vasoconstriction, smooth muscle remodeling, and RV hypertrophy [94,95]. Interestingly, hypoxia-induced activation and membrane translocation of p47phox subunit of Nox2 in pulmonary but not mesenteric arteries [96] suggests the unique function of Nox2 in hypoxic pulmonary vessels compared to the systemic circulation.…”

Section: Sources Of Ros In Pah and The Role Of Gendermentioning

confidence: 99%

Role of Gender in Regulation of Redox Homeostasis in Pulmonary Arterial Hypertension

et al. 2019

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Pulmonary arterial hypertension (PAH) is one of the diseases with a well-established gender dimorphism. The prevalence of PAH is increased in females with a ratio of 4:1, while poor survival prognosis is associated with the male gender. Nevertheless, the specific contribution of gender in disease development and progression is unclear due to the complex nature of the PAH. Oxidative and nitrosative stresses are important contributors in PAH pathogenesis; however, the role of gender in redox homeostasis has been understudied. This review is aimed to overview the possible sex-specific mechanisms responsible for the regulation of the balance between oxidants and antioxidants in relation to PAH pathobiology.

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“…NOX5‐derived ROS have been implicated in a number of pathologies, especially cardiovascular disease, renal disease and cancer. Other pathologies, such as neurodegenerative diseases (Tarafdar & Pula, ), pulmonary arterial hypertension (Peng, Liu, Xu, Peng, & Luo, ) and liver fibrosis (Andueza et al., ), have also been linked to NOX5, but there is very little supporting evidence for this.…”

Section: Pathophysiology 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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NADPH oxidase: its potential role in promotion of pulmonary arterial hypertension

Cited by 21 publications

References 65 publications

Magnesium Lithospermate B Derived from Salvia miltiorrhiza Ameliorates Right Ventricle Remodeling in Pulmonary Hypertensive Rats via Inhibition of NOX/VPO1 Pathway

Magnesium Lithospermate B Derived from Salvia miltiorrhiza Ameliorates Right Ventricle Remodeling in Pulmonary Hypertensive Rats via Inhibition of NOX/VPO1 Pathway

Role of Gender in Regulation of Redox Homeostasis in Pulmonary Arterial Hypertension

NOX5: Molecular biology and pathophysiology

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