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

By G. Drummond, S. Selemidis, K. Griendling, C. Sobey. Nature reviews. Drug discovery, 2011

924 citations recorded by the source corpus.

NADPH oxidases are a family of enzymes that generate reactive oxygen species (ROS). The NOX1 (NADPH oxidase 1) and NOX2 oxidases are the major sources of ROS in the artery wall in conditions such as hypertension, hypercholesterolaemia, diabetes and ageing, and so they are important contributors to the oxidative stress, endothelial dysfunction and vascular inflammation that underlies arterial remodelling and atherogenesis. In this Review, we advance the concept that compared to the use of conventional antioxidants, inhibiting NOX1 and NOX2 oxidases is a superior approach for combating oxidative stress. We briefly describe some common and emerging putative NADPH oxidase inhibitors. In addition, we highlight the crucial role of the NADPH oxidase regulatory subunit, p47phox, in the activity of vascular NOX1 and NOX2 oxidases, and suggest how a better understanding of its specific molecular interactions may enable the development of novel isoform-selective drugs to prevent or treat cardiovascular diseases.

Subfields: Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/e45708f4eeabcc446b374265badc29e9981c5ad4

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Citations in the corpus

Endothelial dysfunction - a major mediator of diabetic vascular disease. (2013, background): “Substances able to inhibit NADPH oxidases and prevent superoxide production may be useful for treatment of endothelial dysfunction [230].”
Mechanisms of diabetic complications. (2013, background): “Although NAD(P)H oxidase as a potential pathogenic mediator of hyperglycemia induced ROS production, there are some major challenges to be overcome when targeting this pathway including redundancy among Nox isoforms (160) and the capacity of pharmacological agents not to interfere with intracellular”
Oxidative stress in angiogenesis and vascular disease. (2014, background): “11 source of ROS in vasculature.(108,109) However, the studies using such inhibitors in vivo animal models(15,16) are limited.”
Upregulated NLRP3 Inflammasome Activation in Patients With Type 2 Diabetes (2012, background): “A number of studies also have indicated that an altered redox potential and oxidative stress are highly associated with risk factors for type 2 diabetes and its complications (33,34).”
The pathobiology of vascular dementia (2013, positive): “…(Miller et al., 2005), has emerges as an important source in vascular oxidative stress in aging, hypertension, hyperlipidemia and diabetes (Faraci et al., 2011), and inhibition or genetic inactivation of this enzyme has been shown to ameliorate the vascular dysfunction (Drummond et al., 2011).”
Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans (2017, background): “Theestablishedrole indiseases ofXO[318]andNOX[319, 320] suggested their pharmacological inhibition in theprevention and treatment of pathologies related to oxidative stress.”
The role of oxidative stress during inflammatory processes (2013, background): “This process has been particularly well described in the context of inflammatory cardiovascular pathologies, most significantly atherosclerosis, as reviewed recently (Forstermann and Li, 2011; Alkaitis and Crabtree, 2012).”