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Antioxidants 2017, 6(2), 40; doi:10.3390/antiox6020040

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

The John A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT 84132, USA
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Author to whom correspondence should be addressed.
Academic Editor: Masuko Ushio-Fukai
Received: 11 April 2017 / Revised: 24 May 2017 / Accepted: 31 May 2017 / Published: 3 June 2017
(This article belongs to the Special Issue ROS Derived from NADPH Oxidase (NOX) in Angiogenesis)
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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. View Full-Text
Keywords: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); NOX2; NOX4; NOX1; NOX5; vascular endothelial cell; angiogenesis; neovascularization; vascular inflammation; oxygen-induced retinopathy; eye; retina nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); NOX2; NOX4; NOX1; NOX5; vascular endothelial cell; angiogenesis; neovascularization; vascular inflammation; oxygen-induced retinopathy; eye; retina
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Wang, H.; Hartnett, M.E. Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects. Antioxidants 2017, 6, 40.

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