Submit to Antioxidants Review for Antioxidants Propose a Special Issue

Journal Browser

ROS Derived from NADPH Oxidase (NOX) in Angiogenesis

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 March 2017) | Viewed by 94626

Share This Special Issue

Special Issue Editor

Prof. Dr. Masuko Ushio-Fukai

E-Mail Website
Guest Editor

Vascular Biology Center, Department of Medicine, Cardiology, Medical College of Georgia at Augusta University, Augusta, GA, USA
Interests: reactive oxygen species; redox signaling; vascular endothelial growth factor; angiogenesis; endothelial cells; peripheral arterial disease; diabetes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Angiogenesis, a process of new blood vessel growth, contributes to normal development, wound healing and treatment of ischemic heart and limb diseases, as well as various pathophysiologies such as cancer, diabetic retinopathy and atherosclerosis. Reactive oxygen species (ROS), such as O₂⁻ and H₂O₂ at excess levels are detrimental and toxic, while , at physiological concentrations, they can act as second messengers to regulate reparative and pathological angiogenesis and vascular repair. Accumulating evidence suggests that ROS derived from NADPH oxidase (NOX), especially NOX4 and NOX2, play an important role in angiogenic signaling via activating redox-sensitive kinases and inactivating protein tyrosine phosphatase via oxidative inactivation of reactive cysteine residues. Furthermore, they are involved in regulating redox-sensitive angiogenic genes, such as HIF1alpha and VEGF in endothelial cells (ECs). The purpose of this Special Issue is to highlight recent progress on the emerging area of the role of ROS derived from NOX4 and NOX2 in angiogenic signaling in ECs, as well as physiological and pathological angiogenesis in vivo and their underlying mechanisms. Suppressing pathological neovascularization in the retina and tumors and enhancing therapeutic angiogenesis—such as wound healing and ischemia- or exercise-induced revascularization by manipulating NOXs, their regulators and ROS targets—appears to be an attractive therapeutic strategy to treat diabetic retinopathy, cancer and ischemic heart and peripheral vascular diseases.

Prof. Dr. Masuko Ushio-Fukai
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Reactive oxygen species
NADPH oxidase
Angiogenesis
Redox signaling
Endothelial cell
Ischemic disease
Wound healing
Cancer
Diabetic retinopathy

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review

15 pages, 2427 KiB

Open AccessArticle

Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis

by Seock-Won Youn, Yang Li, Young-Mee Kim, Varadarajan Sudhahar, Kareem Abdelsaid, Ha Won Kim, Yutao Liu, David J.R. Fulton, Muhammad Ashraf, Yaoliang Tang, Tohru Fukai and Masuko Ushio-Fukai

Antioxidants 2019, 8(1), 18; https://doi.org/10.3390/antiox8010018 - 10 Jan 2019

Cited by 65 | Viewed by 6754

Abstract

Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

3879 KiB

Open AccessArticle

Deletion of TXNIP Mitigates High-Fat Diet-Impaired Angiogenesis and Prevents Inflammation in a Mouse Model of Critical Limb Ischemia

by Sally L. Elshaer, Islam N. Mohamed, Maha Coucha, Sara Altantawi, Wael Eldahshan, Megan L. Bartasi, Ahmed Y. Shanab, Renee Lorys and Azza B. El-Remessy

Antioxidants 2017, 6(3), 47; https://doi.org/10.3390/antiox6030047 - 29 Jun 2017

Cited by 28 | Viewed by 7114

Abstract

Background: Previous work demonstrated that high-fat diet (HFD) triggered thioredoxin-interacting protein (TXNIP) and that silencing TXNIP prevents diabetes-impaired vascular recovery. Here, we examine the impact of genetic deletion of TXNIP on HFD-impaired vascular recovery using hind limb ischemia model. Methods: Wild type mice (WT, C57Bl/6) and TXNIP knockout mice (TKO) were fed either normal chow diet (WT-ND and TKO-ND) or 60% high-fat diet (WT-HFD and TKO-HFD). After four weeks of HFD, unilateral hind limb ischemia was performed and blood flow was measured using Laser doppler scanner at baseline and then weekly for an additional three weeks. Vascular density, nitrative stress, infiltration of CD68+ macrophages, and expression of inflammasome, vascular endothelial growth factor (VEGF), VEGF receptor-2 were examined by slot blot, Western blot and immunohistochemistry. Results: By week 8, HFD caused similar increases in weight, cholesterol and triglycerides in both WT and TKO. At week 4 and week 8, HFD significantly impaired glucose tolerance in WT and to a lesser extent in TKO. HFD significantly impaired blood flow and vascular density (CD31 labeled) in skeletal muscle of WT mice compared to ND but not in TKO. HFD and ischemia significantly induced tyrosine nitration, and systemic IL-1β and infiltration of CD68+ cells in skeletal muscle from WT but not from TKO. HFD significantly increased cleaved-caspase-1 and IL-1 β compared to ND. Under both ND, ischemia tended to increase VEGF expression and increased VEGFR2 activation in WT only but not TKO. Conclusion: Similar to prior observation in diabetes, HFD-induced obesity can compromise vascular recovery in response to ischemic insult. The mechanism involves increased TXNIP-NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome activation, nitrative stress and impaired VEGFR2 activation. Deletion of TXNIP restored blood flow, reduced nitrative stress and blunted inflammasome-mediated inflammation; however, it did not impact VEGF/VEGFR2 in HFD. Targeting TXNIP-NLRP3 inflammasome can provide potential therapeutic target in obesity-induced vascular complication. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

4228 KiB

Open AccessArticle

NOX2-Induced Activation of Arginase and Diabetes-Induced Retinal Endothelial Cell Senescence

by Modesto Rojas, Tahira Lemtalsi, Haroldo A. Toque, Zhimin Xu, David Fulton, Robert William Caldwell and Ruth B. Caldwell

Antioxidants 2017, 6(2), 43; https://doi.org/10.3390/antiox6020043 - 15 Jun 2017

Cited by 49 | Viewed by 7585

Abstract

Increases in reactive oxygen species (ROS) and decreases in nitric oxide (NO) have been linked to vascular dysfunction during diabetic retinopathy (DR). Diabetes can reduce NO by increasing ROS and by increasing activity of arginase, which competes with nitric oxide synthase (NOS) for their commons substrate l-arginine. Increased ROS and decreased NO can cause premature endothelial cell (EC) senescence leading to defective vascular repair. We have previously demonstrated the involvement of NADPH oxidase 2 (NOX2)-derived ROS, decreased NO and overactive arginase in DR. Here, we investigated their impact on diabetes-induced EC senescence. Studies using diabetic mice and retinal ECs treated with high glucose or H₂O₂ showed that increases in ROS formation, elevated arginase expression and activity, and decreased NO formation led to premature EC senescence. NOX2 blockade or arginase inhibition prevented these effects. EC senescence was also increased by inhibition of NOS activity and this was prevented by treatment with a NO donor. These results indicate that diabetes/high glucose-induced activation of arginase and decreases in NO bioavailability accelerate EC senescence. NOX2-generated ROS contribute importantly to this process. Blockade of NOX2 or arginase represents a strategy to prevent diabetes-induced premature EC senescence by preserving NO bioavailability. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 3604 KiB

Open AccessReview

Subcellular Reactive Oxygen Species (ROS) in Cardiovascular Pathophysiology

by Sarah Aldosari, Maan Awad, Elizabeth O. Harrington, Frank W. Sellke and M. Ruhul Abid

Antioxidants 2018, 7(1), 14; https://doi.org/10.3390/antiox7010014 - 16 Jan 2018

Cited by 75 | Viewed by 12755

Abstract

There exist two opposing perspectives regarding reactive oxygen species (ROS) and their roles in angiogenesis and cardiovascular system, one that favors harmful and causal effects of ROS, while the other supports beneficial effects. Recent studies have shown that interaction between ROS in different sub-cellular compartments plays a crucial role in determining the outcomes (beneficial vs. deleterious) of ROS exposures on the vascular system. Oxidant radicals in one cellular organelle can affect the ROS content and function in other sub-cellular compartments in endothelial cells (ECs). In this review, we will focus on a critical fact that the effects or the final phenotypic outcome of ROS exposure to EC are tissue- or organ-specific, and depend on the spatial (subcellular localization) and temporal (duration of ROS exposure) modulation of ROS levels. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

656 KiB

Open AccessReview

The Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Lung Architecture Remodeling

by Anantha Harijith, Viswanathan Natarajan and Panfeng Fu

Antioxidants 2017, 6(4), 104; https://doi.org/10.3390/antiox6040104 - 19 Dec 2017

Cited by 24 | Viewed by 6350

Abstract

Chronic lung disorders, such as pulmonary artery hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and neonatal bronchopulmonary dysplasia (BPD), are characterized by airway and/or vascular remodeling. Despite differences in the pathology, reactive oxygen species (ROS) have been highlighted as a critical contributor to the initiation and development of airway and vascular remodeling. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) appear to play a pivotal role in lung signaling, leading to marked changes in pulmonary airway and vascular cell phenotypes, including proliferation, hypertrophy and apoptosis. In this review, we summarized the current literature regarding the role of Nox in the airway and vascular remodeling. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

2483 KiB

Open AccessReview

Nox, Reactive Oxygen Species and Regulation of Vascular Cell Fate

by Denise Burtenshaw, Roya Hakimjavadi, Eileen M. Redmond and Paul A. Cahill

Antioxidants 2017, 6(4), 90; https://doi.org/10.3390/antiox6040090 - 14 Nov 2017

Cited by 86 | Viewed by 8956

Abstract

The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell fate. The major source of ROS generated within the vascular system is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (Nox), of which seven members have been characterized. The Nox family are critical determinants of the redox state within the vessel wall that dictate, in part the pathophysiology of several vascular phenotypes. This review highlights the putative role of ROS in controlling vascular fate by promoting endothelial dysfunction, altering vascular smooth muscle phenotype and dictating resident vascular stem cell fate, all of which contribute to intimal medial thickening and vascular disease progression. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

739 KiB

Open AccessReview

NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease

by Pradeep Manuneedhi Cholan, Siân P. Cartland and Mary M. Kavurma

Antioxidants 2017, 6(3), 56; https://doi.org/10.3390/antiox6030056 - 12 Jul 2017

Cited by 10 | Viewed by 6864

Abstract

Peripheral artery disease (PAD) is caused by narrowing of arteries in the limbs, normally occurring in the lower extremities, with severe cases resulting in amputation of the foot or leg. A potential approach for treatment is to stimulate the formation of new blood vessels to restore blood flow to limb tissues. This is a process called angiogenesis and involves the proliferation, migration, and differentiation of endothelial cells. Angiogenesis can be stimulated by reactive oxygen species (ROS), with NADPH oxidases (NOX) being a major source of ROS in endothelial cells. This review summarizes the recent evidence implicating NOX isoforms in their ability to regulate angiogenesis in vascular endothelial cells in vitro, and in PAD in vivo. Increasing our understanding of the involvement of the NOX isoforms in promoting therapeutic angiogenesis may lead to new treatment options to slow or reverse PAD. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

1093 KiB

Open AccessReview

Reactive Oxygen and Nitrogen Species in the Development of Pulmonary Hypertension

by David J.R. Fulton, Xueyi Li, Zsuzsanna Bordan, Stephen Haigh, Austin Bentley, Feng Chen and Scott A. Barman

Antioxidants 2017, 6(3), 54; https://doi.org/10.3390/antiox6030054 - 06 Jul 2017

Cited by 61 | Viewed by 9247

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature that involves the loss of endothelial function together with inappropriate smooth muscle cell growth, inflammation, and fibrosis. These changes underlie a progressive remodeling of blood vessels that alters flow and increases pulmonary blood pressure. Elevated pressures in the pulmonary artery imparts a chronic stress on the right ventricle which undergoes compensatory hypertrophy but eventually fails. How PAH develops remains incompletely understood and evidence for the altered production of reactive oxygen and nitrogen species (ROS, RNS respectively) in the pulmonary circulation has been well documented. There are many different types of ROS and RNS, multiple sources, and collective actions and interactions. This review summarizes past and current knowledge of the sources of ROS and RNS and how they may contribute to the loss of endothelial function and changes in smooth muscle proliferation in the pulmonary circulation. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

950 KiB

Open AccessReview

The Role of NOX4 and TRX2 in Angiogenesis and Their Potential Cross-Talk

by Chaofei Chen, Li Li, Huanjiao Jenny Zhou and Wang Min

Antioxidants 2017, 6(2), 42; https://doi.org/10.3390/antiox6020042 - 08 Jun 2017

Cited by 34 | Viewed by 10295

Abstract

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family is the major source of reactive oxygen species (ROS) in the vascular system. In this family, NOX4, a constitutive active form of NOXs, plays an important role in angiogenesis. Thioredoxin 2 (TRX2) is a key mitochondrial redox protein that maintains normal protein function and also provides electrons to peroxiredoxin 3 (PRX3) to scavenge H₂O₂ in mitochondria. Angiogenesis, a process of new blood vessel formation, is involved in a variety of physiological processes and pathological conditions. It seems to be paradoxical for ROS-producing NOX4 and ROS-scavenging TRX2 to have a similar role in promoting angiogenesis. In this review, we will focus on data supporting the role of NOX4 and TRX2 in angiogenesis and their cross-talks and discuss how ROS can positively or negatively regulate angiogenesis, depending on their species, levels and locations. NOX4 and TRX2-mediated ROS signaling could be promising targets for the treatment of angiogenesis-related diseases. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

1871 KiB

Open AccessReview

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

by Haibo Wang and M. Elizabeth Hartnett

Antioxidants 2017, 6(2), 40; https://doi.org/10.3390/antiox6020040 - 03 Jun 2017

Cited by 34 | Viewed by 7822

Abstract

Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures

Figure 1

853 KiB

Open AccessReview

The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis

by Rodrigo Prieto-Bermejo and Angel Hernández-Hernández

Antioxidants 2017, 6(2), 32; https://doi.org/10.3390/antiox6020032 - 13 May 2017

Cited by 49 | Viewed by 9786

Abstract

Eukaryotic cells have to cope with the constant generation of reactive oxygen species (ROS). Although the excessive production of ROS might be deleterious for cell biology, there is a plethora of evidence showing that moderate levels of ROS are important for the control of cell signaling and gene expression. The family of the nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases or Nox) has evolved to produce ROS in response to different signals; therefore, they fulfil a central role in the control of redox signaling. The role of NADPH oxidases in vascular physiology has been a field of intense study over the last two decades. In this review we will briefly analyze how ROS can regulate signaling and gene expression. We will address the implication of NADPH oxidases and redox signaling in angiogenesis, and finally, the therapeutic possibilities derived from this knowledge will be discussed. Full article

(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)

► Show Figures