Coordination between NADPH oxidase and vascular peroxidase 1 promotes dysfunctions of endothelial progenitor cells in hypoxia-induced pulmonary hypertensive rats

Wang, E-Li; Jia, Miaomiao; Luo, Fang; Li, Tao; Peng, Junwen; Luo, Xiu-Ju; Song, Fenglin; Yang, Jinfu; Peng, Jun; Liu, Bin

doi:10.1016/j.ejphar.2019.172459

Cited by 14 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is also evidence of NOX2 involvement in the pathogenesis of pulmonary hypertension. NOX2 protein is elevated in endothelial progenitor cells in hypoxia-induced PH in rats [ 74 ]. Hypoxic pulmonary hypertension is attenuated in NOX2 deleted mice together with superoxide production in the pulmonary vasculature, reduced pulmonary vascular resistance and right ventricular hypertrophy [ 43 ].…”

Section: The X Chromosome In Pulmonary Hypertensionmentioning

confidence: 99%

Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Kostyunina

McLoughlin

2021

Antioxidants

View full text Add to dashboard Cite

Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.

show abstract

Section: The X Chromosome In Pulmonary Hypertensionmentioning

confidence: 99%

Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Kostyunina

McLoughlin

2021

Antioxidants

View full text Add to dashboard Cite

show abstract

“…Multiple studies reported that PXDN contributes to pathological procedure of cardiovascular diseases such as vascular calcification, hypertension and cardiac hypertrophy [ 18 , 44 , 45 ]. Especially, our former researches have demonstrated that PXDN plays a key role in the endothelial cell senescence, apoptosis and endothelial progenitor cell dysfunction [ [46] , [47] , [48] , [49] , [50] ]. What's more, the preliminary research found that PXDN showed a significant function in regulating eNOS expression and activity [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, NOX2-specific inhibitor significantly reduced ROS production in the aortas and mesenteric arteries of db/db mice compared to non-specific NOX inhibitor and mitochondrial ROS scavenger. Previous studies have found that the NOX2/PXDN pathway is involved in a series of pathophysiological processes including hypoxia-induced vascular remodeling and angiotensin II-induced myocardial hypertrophy [ 45 , 71 ]. Based on the high expression and cellular localization of NOX2 in db/db mice, we hypothesized NOX2 may participates in PXDN-mediated endothelial dysfunction induced by AGEs.…”

Section: Discussionmentioning

confidence: 99%

Peroxidasin promotes diabetic vascular endothelial dysfunction induced by advanced glycation end products via NOX2/HOCl/Akt/eNOS pathway

et al. 2021

View full text Add to dashboard Cite

Reactive oxygen species (ROS) derived from NADPH oxidases (NOX) plays an essential role in advanced glycation end products (AGEs)-induced diabetic vascular endothelial dysfunction. Peroxidasin (PXDN, VPO1) is one member of peroxidases family that catalyzes hydrogen peroxide (H 2 O 2 ) to hypochlorous acid (HOCl). This present study aimed to elucidate the role of PXDN in promoting vascular endothelial dysfunction induced by AGEs in diabetes mellitus. We found that, compared to non-diabetic (db/m) mice, PXDN expression was notably increased in db/db mice with impaired endothelium-dependent relaxation. Knockdown of PXDN in vivo through tail vein injection of siRNA restored the impaired endothelium-dependent relaxation function of db/db mice which is accompanied with up-regulation of eNOS Ser1177 phosphorylation and NO production. AGEs significantly elevated expression of PXDN and 3-Cl-Tyr, but decreased phosphorylation of Akt and eNOS and NO release in HUVECs. All these effects induced by AGEs were remarkable alleviated by silencing PXDN with small interfering RNAs. In addition, HOCl treatment alone as well as HOCl added with Akt inhibitor MK2206 inhibited phosphorylation of Akt and eNOS, reducing NO production. More importantly,AGEs-induced up-regulation of PXDN and 3-Cl-Tyr with endothelial dysfunction were transformed by NOX2 silencing and H 2 O 2 scavengers. Thus, these results support the conclusion that PXDN promotes AGEs-induced diabetic vascular endothelial dysfunction by attenuating eNOS phosphorylation at Ser1177 via NOX2/HOCl/Akt pathway.

show abstract

“…The staining with Hematoxylin-eosin (HE), Wheat germ agglutinin (WGA), Sirius red, Masson’ trichrome (Masson), or Verhoeff elastic van Gieson (EVG) was performed to evaluate the morphological changes of the RV tissues. The procedures were conducted as described in our previous studies ( Liu et al, 2014 ; Li et al, 2019a ; Wang et al, 2019 ). Briefly, for HE staining, the paraffin sections were stained with HE staining solution (Servicebio, Wuhan, China) for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Magnolol Attenuates Right Ventricular Hypertrophy and Fibrosis in Hypoxia-Induced Pulmonary Arterial Hypertensive Rats Through Inhibition of the JAK2/STAT3 Signaling Pathway

Luo

Wang

et al. 2021

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol (6, 6′, 7, 12-tetramethoxy-2,2′-dimethyl-1-β-berbaman, C18H18O2) is a compound isolated from Magnolia Officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. In vivo, male Sprague Dawley rats were exposed to 10% O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of Fulton index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3; these changes were attenuated by treating with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3% O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagen Ⅰ, collagen Ⅲ, and α-SMA). Administration of magnolol and TG-101348 or JSI-124 (both JAK2 selective inhibitors) could prevent myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. Based on these observations, we conclude that magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway. Magnolol may possess the potential clinical value for PAH therapy.

show abstract

Coordination between NADPH oxidase and vascular peroxidase 1 promotes dysfunctions of endothelial progenitor cells in hypoxia-induced pulmonary hypertensive rats

Cited by 14 publications

References 26 publications

Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes

Peroxidasin promotes diabetic vascular endothelial dysfunction induced by advanced glycation end products via NOX2/HOCl/Akt/eNOS pathway

Magnolol Attenuates Right Ventricular Hypertrophy and Fibrosis in Hypoxia-Induced Pulmonary Arterial Hypertensive Rats Through Inhibition of the JAK2/STAT3 Signaling Pathway

Contact Info

Product

Resources

About