Endothelial NADPH oxidase

Xanthine oxidase is not the only source of reactive species in ischemia-reoxygenation injury. Another source of oxygen radicals is NADPH oxidase. For example, it has been shown that endothelial NADPH oxidase produced reactive oxygen species in lungs exposed to ischemia [13]. (The role of NADPH oxidase as a producer of oxygen radicals in tissue is considered below.)... 

Steffen Y, Gruber C, Schewe T, Sies H. 2008. Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase. Arch Biochem Biophys 469 209-219. 

Isorhamnetin Inihibiton of endothelial NADPH oxidase Steffen et al., 2008... 

Liu J Q, Zelko I N, Eolz R J (2004). Reoxygenation-induced constriction in murine coronary arteries the role of endothelial NADPH oxidase (gp91phox) and intracellular superoxide. 7. Biol. Chem. 279 24493-24497. 

Fisher, A.B., Al-Mehdi, A.B., and Muzykantov, V., Activation of endothelial NADPH oxidase as the source of a reactive oxygen species in lung ischemia. Chest, 116 (Suppl. 1), 25S, 1999. 

Recently, the biological impact of dietary polyphenols has been associated with the endothelial metabolism of NO. In particular, it has been shown that mono-O-methylated flavanols and other flavonoids by inhibition of endothelial NADPH oxidase suppress the formation of superoxide radical, that otherwise eliminates NO via diffusion-controlled formation of peroxynitrite (Steffen et al, 2008). Such a mechanism, preserving or enhancing the bioavailability of NO, may underlie the improvement of vascular endothelial function by certain flavonoid structures and its metabolites via, for instance, dilation of arterial vessels and lowering of blood pressure (Steffen et al, 2008). 

There are various angiotensin II-dependent pathways of NADPH oxidase activation. Xie et al. [116] have found that angiotensin II induced the stimulation of osteopontin, an extracellular matrix protein, in cardiac microvascular endothelial... 

Holland et al. [125] have shown that the potent vascular smooth muscle cell mitogen and phospholipase A2 activator thrombin stimulated superoxide production in human endothelial cells, which was inhibited by the NADPH oxidase inhibitors. Similarly, thrombin enhanced the production of oxygen species and the expression of )Alphos and Rac2 subunits of NADPH oxidase in VSMCs [126,127]. Greene et al. [128] demonstrated that the activator of NO synthase neuropeptide bradykinin is also able to stimulate NADPH oxidase in VSMCs. Similar to XO, NADPH oxidase enhanced superoxide production in pulmonary artery smooth muscle cells upon exposure to hypoxia [129]. 

Oxidized LDL are considered to be one of the major factors associated with the development of atherosclerosis. The earliest event is the transport of LDL into the arterial wall where LDL, being trapped in subendothelial space, are oxidized by oxygen radicals produced by endothelial and arterial smooth muscle cells. The oxidation of LDL in the arterial wall is affected by various factors including hemodynamic forces such as shear stress and stretch force. Thus, it has been shown [177] that stress force imposed on vascular smooth muscle cells incubated with native LDL increased the MDA formation by about 150% concomitantly with the enhancement of superoxide production. It was suggested that oxidation was initiated by NADPH oxidase-produced superoxide and depended on the presence of metal ions. 

It has been found that the 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) inhibitors statins (atorvastatin, pravastatin, and cerivastatin), widely prescribed cholesterol-lowering agents, are able to inhibit phorbol ester-stimulated superoxide formation in endothelial-intact segments of the rat aorta [64] and suppress angiotensin II-mediated free radical production [65]. Delbose et al. [66] found that statins inhibited NADPH oxidase-catalyzed PMA-induced superoxide production by monocytes. It was suggested that statins can prevent or limit the involvement of superoxide in the development of atherosclerosis. It is important that statin... 

Furthermore, as already mentioned above, the interaction of superoxide with NO synthase in vascular tissue may lead to uncoupling of this enzyme and increasing superoxide production [117]. Therefore, the overproduction of superoxide may affect superoxide/nitric oxide by different ways, resulting in cell injury. It is interesting that some biomolecules may be useful for improving this balance. Thus, 17(3-estradiol upregulated NO synthase expression and inhibited NADPH oxidase expression in human endothelial cells [136]. 

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