Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets

Drummond, Grant Raymond; Selemidis, Stavros; Griendling, Kathy K.; Sobey, Christopher G.

doi:10.1038/nrd3403

Cited by 797 publications

(829 citation statements)

References 225 publications

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“…In addition to the fact that CS contains a high concentration of reactive oxygen species (ROS), activated leukocytes also produce large amounts of ROS, with one such example being the superoxide anions produced via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 8 . In contrast to this, the body contains a number of endogenous antioxidant proteins such as superoxide dismutase (SOD) and glutathione S-transferase (GST), with a decrease in these proteins reported to be involved in the pathogenesis of COPD 9,10 .…”

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confidence: 99%

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

et al. 2013

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The clinical treatment of chronic obstructive pulmonary disease (COPD) requires not only an improvement of airflow by bronchodilation but also the suppression of emphysema by controlling inflammation. Here we screen a compound library consisting of clinically used drugs for their ability to prevent elastase-induced airspace enlargement in mice. We show that intratracheal administration or inhalation of mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders, decreases the severity of elastase-induced airspace enlargement and respiratory dysfunction. Although mepenzolate bromide shows bronchodilatory activity, most other muscarinic antagonists do not improve elastase-induced pulmonary disorders. Apart from suppressing elastase-induced pulmonary inflammatory responses and the production of superoxide anions, mepenzolate bromide reduces the level of cigarette smoke-induced airspace enlargement and respiratory dysfunction. Based on these results, we propose that mepenzolate bromide may be an effective therapeutic for the treatment of COPD due to its anti-inflammatory and bronchodilatory activities.

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confidence: 99%

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

et al. 2013

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“…This leads to oxidative stress, triggering molecular processes, which, in the vasculature, contributes to vascular injury and inflammation. The Noxs have been extensively reviewed (7,16,53,82,113,160), and only an overview of recent developments is discussed here, focusing on the most recently characterized isoform, Nox5.…”

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confidence: 99%

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

232

177

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Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

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“…Therefore, targeting ROS production by blocking the activity of some enzymes -such as NADPH oxidase -is likely to be a far superior approach for combating oxidative stress and preventing the progression of vascular disease than previous attempts aimed at scavenging ROS 33 .…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress in carotid arteries of patients submitted to carotid endarterectomy. The role of aging process

et al. 2016

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PURPOSE:To evaluated the role of oxidative stress on aging process in patients submitted to carotid endarterectomy. METHODS:Twenty patients were divided into two groups: older group (≥ 70 years old); and the younger group (< 70 years old).We evaluated the reactive oxygen species (ROS) concentration, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, superoxide dismutase (SOD) and catalase (CAT) activities as so as nitrite levels in fragments of carotid arteries harvested during carotid endarterectomy for treatment of high grade carotid stenosis. RESULTS:We observed a higher levels of ROS and NADPH oxidase activity in the older group (p<0.05). Furthermore, the nitrite concentration was lower in the older group (14.55 ± 5.61 x 10 -3 versus 26.42 ± 8.14 x 10 -3 µM; p=0.0123). However, the activities of antioxidant enzymes (CAT and SOD) were similar in both the groups. CONCLUSIONS:Arterial aging is associated with increased concentrations of oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity as so as nitrite reduction in human carotid artery specimens. Maybe therapies that block NADPH oxidase activity and enhance nitrite stores would be a good strategy to reduce the effect of oxidative stress in arterial aging.Key words: Oxidative Stress. Reactive Oxygen Species. Carotid Arteries. Endarterectomy, Carotid.Oxidative stress in carotid arteries of patients submitted to carotid endarterectomy. The role of aging process

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Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets

Cited by 797 publications

References 225 publications

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Oxidative stress in carotid arteries of patients submitted to carotid endarterectomy. The role of aging process

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