NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease

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.

• Publication year

  2017

• Venue

  Antioxidants

• Publication date

  2017-07-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/antiox6030056PMID 28704938PMCID 5618084
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• NOX2, NOX4, and mitochondrial-derived reactive oxygen species contribute to angiopoietin-1 signaling and angiogenic responses in endothelial cells.

  2017cited by this paper
• Mitochondrial redox plays a critical role in the paradoxical effects of NAPDH oxidase-derived ROS on coronary endothelium

  2017cited by this paper
• Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis

  2017cited by this paper
• Endothelial Nox1 oxidase assembly in human pulmonary arterial hypertension; driver of Gremlin1-mediated proliferation.

  2017cited by this paper
• Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice

  2016cited by this paper
• NOX4 downregulation leads to senescence of human vascular smooth muscle cells

  2016cited by this paper
• Role of ROS and RNS Sources in Physiological and Pathological Conditions

  2016cited by this paper
• Nox2 contributes to the arterial endothelial specification of mouse induced pluripotent stem cells by upregulating Notch signaling

  2016cited by this paper
• The NADPH Oxidase Nox4 mediates tumour angiogenesis

  2016cited by this paper
• Differential Roles of Protein Complexes NOX1-NOXO1 and NOX2-p47phox in Mediating Endothelial Redox Responses to Oscillatory and Unidirectional Laminar Shear Stress*

  2016cited by this paper
• Lipopolysaccharide (LPS)-mediated Angiopoietin-2-dependent Autocrine Angiogenesis Is Regulated by NADPH Oxidase 2 (Nox2) in Human Pulmonary Microvascular Endothelial Cells*

  2015cited by this paper
• Tumor Necrosis Factor–Related Apoptosis‐Inducing Ligand (TRAIL) Promotes Angiogenesis and Ischemia‐Induced Neovascularization Via NADPH Oxidase 4 (NOX4) and Nitric Oxide–Dependent Mechanisms

  2015cited by this paper
• Both hydrogen peroxide and transforming growth factor beta 1 contribute to endothelial Nox4 mediated angiogenesis in endothelial Nox4 transgenic mouse lines.

  2014cited by this paper
• Molecular diagnosis of chronic granulomatous disease

  2014cited by this paper
• Oxidative stress in angiogenesis and vascular disease.

  2014cited by this paper
• Polymerase &dgr;-Interacting Protein 2 Promotes Postischemic Neovascularization of the Mouse Hindlimb

  2014cited by this paper
• Assessment of Atherosclerosis in Chronic Granulomatous Disease

  2014cited by this paper
• Endothelial NADPH oxidase 4 mediates vascular endothelial growth factor receptor 2–induced intravitreal neovascularization in a rat model of retinopathy of prematurity

  2014influential reference
• Control of endothelial function and angiogenesis by PGC-1α relies on ROS control of vascular stability.

  2014cited by this paper
• Nox2 and p47(phox) modulate compensatory growth of primary collateral arteries.

  2014cited by this paper
• Lower extremity amputation in peripheral artery disease: improving patient outcomes

  2014cited by this paper
• Nox4: A Hydrogen Peroxide-Generating Oxygen Sensor

  2014cited by this paper
• ROS function in redox signaling and oxidative stress.

  2014cited by this paper
• Regulation of NADPH-dependent Nitric Oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive NADPH analogue

  2014cited by this paper
• Endothelial NADPH oxidases: which NOX to target in vascular disease?

  2014cited by this paper
• Pharmacological inhibition of NOX reduces atherosclerotic lesions, vascular ROS and immune–inflammatory responses in diabetic Apoe−/− mice

  2014cited by this paper
• NADPH Oxidase–Generated Reactive Oxygen Species Are Required for Stromal Cell–Derived Factor-1&agr;–Stimulated Angiogenesis

  2014cited by this paper
• Polymerase delta-Interacting Protein 2 Promotes Postischemic Neovascularization of the Mouse Hindlimb

  2014influential reference
• Transforming growth factor-β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo

  2014cited by this paper
• Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization.

  2014influential reference
• Nox4 Is a Major Source of Superoxide Production in Human Brain Pericytes

  2014cited by this paper
• NADPH oxidase mediates TNF-α-evoked in vitro brain barrier dysfunction: roles of apoptosis and time.

  2014cited by this paper
• Vascular oxidative stress, nitric oxide and atherosclerosis.

  2014cited by this paper
• Smad-independent pathway involved in transforming growth factor β1-induced Nox4 expression and proliferation of endothelial cells

  2014cited by this paper
• Dark Chocolate Acutely Improves Walking Autonomy in Patients With Peripheral Artery Disease

  2014cited by this paper
• Poldip2 Knockout Results in Perinatal Lethality, Reduced Cellular Growth and Increased Autophagy of Mouse Embryonic Fibroblasts

  2014cited by this paper
• NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis

  2013cited by this paper
• NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease.

  2013cited by this paper
• Perivascular cells in blood vessel regeneration

  2013cited by this paper
• RETRACTED: High Glucose Induced Oxidative Stress and Apoptosis in Cardiac Microvascular Endothelial Cells Are Regulated by FoxO3a

  2013cited by this paper
• Aiding and abetting roles of NOX oxidases in cellular transformation

  2012cited by this paper
• The HIF1 target gene NOX2 promotes angiogenesis through urotensin-II

  2012influential reference
• Nox4- and Nox2-dependent oxidant production is required for VEGF-induced SERCA cysteine-674 S-glutathiolation and endothelial cell migration.

  2012cited by this paper
• NADPH Oxidase 2 Regulates Bone Marrow Microenvironment Following Hindlimb Ischemia: Role in Reparative Mobilization of Progenitor Cells

  2012influential reference
• Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration.

  2012cited by this paper
• Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase

  2012cited by this paper
• The role of pericytes in angiogenesis.

  2011cited by this paper
• Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR.

  2011influential reference
• The E-loop Is Involved in Hydrogen Peroxide Formation by the NADPH Oxidase Nox4*

  2011cited by this paper
• Calcium/Calmodulin-Dependent Kinase II Mediates the Phosphorylation and Activation of NADPH Oxidase 5

  2011cited by this paper
• Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism

  2011influential reference
• NADPH Oxidase 4 Promotes Endothelial Angiogenesis Through Endothelial Nitric Oxide Synthase Activation

  2011influential reference
• Correction: Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism

  2011cited by this paper
• Hypoxia-induced angiogenesis: good and evil.

  2011influential reference
• Superoxide is a potential culprit of caspase-3 dependent endothelial cell death induced by lysophosphatidylcholine.

  2010cited by this paper
• Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 5 (Nox5) Regulation by Angiotensin II and Endothelin-1 Is Mediated via Calcium/Calmodulin-Dependent, Rac-1–Independent Pathways in Human Endothelial Cells

  2010cited by this paper
• Variations in surgical procedures for hind limb ischaemia mouse models result in differences in collateral formation.

  2010cited by this paper
• Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in vitro and the in vivo expressions of CXCL12 variants and CXCR4 in human critical leg ischemia.

  2010cited by this paper
• Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation

  2009cited by this paper
• NADPH oxidases 1 and 4 mediate cellular senescence induced by resveratrol in human endothelial cells.

  2009cited by this paper
• NADPH oxidase isoform selective regulation of endothelial cell proliferation and survival

  2009cited by this paper
• Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells

  2009cited by this paper
• Roles of Nox1 and other Nox isoforms in cancer development

  2009cited by this paper
• Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system

  2009cited by this paper
• Reactive oxygen species promote angiogenesis in the infarcted rat heart

  2009cited by this paper
• Poldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells

  2009influential reference
• NADPH Oxidase-Dependent Signaling in Endothelial Cells: Role in Physiology and Pathophysiology

  2009cited by this paper
• Regulation of NADPH Oxidase in Vascular Endothelium: The Role of Phospholipases, Protein Kinases, and Cytoskeletal Proteins

  2009cited by this paper
• Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy.

  2008cited by this paper
• Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells.

  2008cited by this paper
• Expression, regulation and function of trail in atherosclerosis.

  2008cited by this paper
• Nox1 Mediates Basic Fibroblast Growth Factor–Induced Migration of Vascular Smooth Muscle Cells

  2007influential reference
• Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor.

  2007cited by this paper
• Important Role of Nox4 Type NADPH Oxidase in Angiogenic Responses in Human Microvascular Endothelial Cells In Vitro

  2007cited by this paper
• Nox 4 regulation of vascular smooth muscle cell differentiation marker gene expression.

  2007cited by this paper
• NOX5 variants are functionally active in endothelial cells.

  2007cited by this paper
• NADPH oxidase modulates myocardial Akt, ERK1/2 activation, and angiogenesis after hypoxia-reoxygenation.

  2007influential reference
• Urokinase Plasminogen Activator Stimulates Vascular Smooth Muscle Cell Proliferation Via Redox-Dependent Pathways

  2006cited by this paper
• NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes.

  2006cited by this paper
• Angiopoietin-1-induced angiogenesis is modulated by endothelial NADPH oxidase.

  2006influential reference
• NOX2 and NOX4 Mediate Proliferative Response in Endothelial Cells

  2006cited by this paper
• Endothelial-cell apoptosis induced by cleaved high-molecular-weight kininogen (HKa) is matrix dependent and requires the generation of reactive oxygen species.

  2006cited by this paper
• Oxidative stress and atherosclerosis.

  2006cited by this paper
• Risk of mortality and cardiovascular disease associated with the ankle-brachial index: Systematic review.

  2006cited by this paper
• The United States Preventive Services Task Force Recommendation Statement on Screening for Peripheral Arterial Disease: More Harm Than Benefit?

  2006cited by this paper
• Search for appropriate experimental methods to create stable hind-limb ischemia in mouse.

  2006cited by this paper
• The superoxide‐producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells

  2005cited by this paper
• The role of pericytes in blood-vessel formation and maintenance.

  2005cited by this paper
• Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats

  2005cited by this paper
• Role of gp91phox (Nox2)-Containing NAD(P)H Oxidase in Angiogenesis in Response to Hindlimb Ischemia

  2005cited by this paper
• Genetic and biochemical background of chronic granulomatous disease.

  2004cited by this paper
• Systemic Regulation of Vascular NAD(P)H Oxidase Activity and Nox Isoform Expression in Human Arteries and Veins

  2004cited by this paper
• Oxidative Stress and Vascular Disease

  2004cited by this paper
• Reactive oxygen species as mediators of angiogenesis signaling. Role of NAD(P)H oxidase

  2004cited by this paper
• Angiogenesis Induced by Endothelial Nitric Oxide Synthase Gene Through Vascular Endothelial Growth Factor Expression in a Rat Hindlimb Ischemia Model

  2003cited by this paper
• Regulation of angiogenesis by hypoxia: role of the HIF system

  2003cited by this paper
• Role of nitric oxide in the modulation of angiogenesis.

  2003cited by this paper
• Reactive oxygen species and hormonal control of cell death.

  2003cited by this paper
• Expression of a Functionally Active gp91phox-Containing Neutrophil-Type NAD(P)H Oxidase in Smooth Muscle Cells From Human Resistance Arteries: Regulation by Angiotensin II

  2002influential reference
• Upregulation of Nox‐Based NAD(P)H Oxidases in Restenosis After Carotid Injury

  2002influential reference

• NADPH Oxidases: Redox Regulation of Cell Homeostasis & Disease.

  2025cites this paper
• Superoxide Anion Generation, Its Pathological Cellular and Molecular Roles and Pharmacological Targeting in Inflammatory Pain: Lessons from the Potassium Superoxide Model

  2025cites this paper
• CD8 + T Cells Negatively Modulate Ischemia‐Induced Angiogenesis in Mice

  2025cites this paper
• Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells

  2021cites this paper
• Canagliflozin is a potential cardioprotective drug but exerts no significant effects on pirarubicin‑induced cardiotoxicity in rats.

  2021cites this paper
• Reducing oxidative stress may be important for treating pirarubicin-induced cardiotoxicity with schisandrin B

  2021cites this paper
• Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease

  2021influential citation
• Dynamic regulation of NADPH oxidase 5 by intracellular heme levels and cellular chaperones

  2020cites this paper
• Role of Subcellular ROS in Providing Resilience to Vascular Endothelium

  2020cites this paper
• Endothelial Cells (ECs) Metabolism: A Valuable Piece to Disentangle Cancer Biology.

  2020cites this paper
• Vascular transcriptome landscape of Trail−/− mice: Implications and therapeutic strategies for diabetic vascular disease

  2020cites this paper
• TRAIL-Expressing Monocyte/Macrophages Are Critical for Reducing Inflammation and Atherosclerosis

  2019cites this paper
• Oxidant-Dependent and Oxidant-Independent Proangiogenic and Vasomotor Signaling in Coronary Vascular Endothelium

  2019cites this paper
• The role of reactive oxygen species in angiogenesis and preventing tissue injury after brain ischemia.

  2019cites this paper
• The role of CFTR in normal human lung microvascular endothelial cells

  2019cites this paper
• NOX-Mediated Oxidation in the Regulation of Cytoskeleton-Related Activities

  2018cites this paper
• TRAIL protects against endothelial dysfunction in vivo and inhibits angiotensin‐II‐induced oxidative stress in vascular endothelial cells in vitro

  2018cites this paper
• How to cite in APA

  year unknowncites this paper