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

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.

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate

“…Currently, a large amount of research has been devoted to the search for, and study of, pharmacological agents with antioxidant effects for the correction of retinal ischemic injury [41][42][43]. According to some authors, during the early phase of an ischemic attack, an increase in extracellular glutamate activates N-methyl-D-aspartate (NMDA) receptors, causing a Ca 2+ influx due to activated NMDA receptors.…”

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

“…In phagocytic cells, ROS play a role in host‐defense responses, and in nonphagocytic cells, ROS control cell differentiation, proliferation, apoptosis, and senescence 1, 2. In the vascular system, ROS regulate vasculogenesis, endothelial function, and vascular tone 3, 4. In cardiovascular diseases, such as hypertension,5 atherosclerosis,6 and pulmonary arterial hypertension,7 Nox‐derived ROS generation is increased, leading to endothelial dysfunction and vascular injury.…”

“…Vascular Noxs have different functions in pathological conditions. Nox1 and Nox2 play a role in angiogenesis and atherosclerosis,3, 6 and Nox4 seems to be vasoprotective in ischemic and hypoxic conditions,10 but injurious in diabetes mellitus, where it promotes vascular fibrosis, diabetic nephropathy, and intravitreal neovascularization 11. Although Nox5 is expressed in mammalian vessels,12, 13, 14 there is a paucity of information on its role and biological significance in the cardiovascular system.…”

Regulatory Influence of Blood Monocytes on the Population Composition of Granulocytes and the State of Their Respiratory Burst in the Widespread Purulent Peritonitis

“…Состояние дыхательного взрыва гранулоцитов крови было оценивалось по хемилюминесцентной реакции с двумя индикаторами -люцигенином и люминолом. Люцигенинзависимая хемилюминесценция отражает уровень синтеза супероксид-радикала, относящийся к первичным АФК, который синтезируется мембранной НАДФН-оксидазой [18,30]. Супероксид-радикал является наиболее бактерицидной АФК, но уровень цитотоксичности гранулоцитов также зависит и от вторичных АФК (гидроксильный радикал, перекись водорода и др.).…”

“…Индекс активации характеризует уровень метаболических резервов клеток, которые определяют возможность до-полнительной индукции респираторного взрыва [5]. В частности, для стимуляции активности НАДФН-оксидазы необходимо повышение активности пентозофосфатного цикла и его субстратное наполнение [18,30].…”