Role of NADPH oxidases in the control of vascular gene expression.

All vascular cells, including endothelial cells and smooth muscle cells, express components of the leukocyte NADPH oxidase such as p22phox, p47phox, and Rac. Endothelial cells and fibroblasts also express the leukocyte NADPH oxidase subunit gp91phox/nox2, whereas in smooth muscle cells nox1 and nox4 are found. The different vascular NADPH oxidases represent important sources for the basal as well as the agonist-induced superoxide anion (O(2) .-) generation in the vasculature. In vascular smooth muscle cells, activation of the NADPH oxidases and the subsequent formation of O(2) .- has been demonstrated for various agents including angiotensin II, thrombin, lysophosphatidylcholine, and tumor necrosis factor alpha. By influencing the activity of p38 mitogen-activated protein kinase and AKT, NADPH oxidase-derived O(2) .- increases the expression of several pro-arteriosclerotic genes, such as monocyte chemoattractant protein-1, tissue factor, and vascular endothelial growth factor. Thus, the vascular NADPH oxidases play an important role in mediating the signal transduction cascade of pro-arteriosclerotic stimuli.