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- W2057751906 abstract "Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play important roles in vascular activation. The p22phox subunit is necessary for the activity of NADPH oxidase complexes utilizing Nox1, Nox2, Nox3, and Nox4 catalytic subunits. We assessed p22phox-deficient mice and human tissue for altered vascular activation. Mice deficient in p22phox were smaller than their wild-type littermates but showed no alteration in basal blood pressure. The wild-type littermates were relatively resistant to forming intimal hyperplasia following carotid ligation, and the intimal hyperplasia that developed was not altered by p22phox deficiency. However, at the site of carotid artery ligation, the p22phox-deficient mice showed significantly less vascular elastic fiber loss compared with their wild-type littermates. This preservation of elastic fibers was associated with a reduced matrix metallopeptidase (MMP) 12/tissue inhibitor of metalloproteinase (TIMP) 1 expression ratio. A similar decrease in the relative MMP12/TIMP1 expression ratio occurred in human coronary artery smooth muscle cells upon knockdown of the hydrogen peroxide responsive kinase CK1αLS. In the ligated carotid arteries, the p22phox-deficient mice showed reduced expression of heterogeneous nuclear ribonucleoprotein C (hnRNP-C), suggesting reduced activity of CK1αLS. In a lung biopsy from a human patient with p22phox deficiency, there was also reduced vascular hnRNP-C expression. These findings indicate that NADPH oxidase complexes modulate aspects of vascular activation including vascular elastic fiber loss, the MMP12/TIMP1 expression ratio, and the expression of hnRNP-C. Furthermore, these findings suggest that the effects of NADPH oxidase on vascular activation are mediated in part by protein kinase CK1αLS." @default.
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- W2057751906 date "2014-01-01" @default.
- W2057751906 modified "2023-10-16" @default.
- W2057751906 title "Altered vascular activation due to deficiency of the NADPH oxidase component p22phox" @default.
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- W2057751906 doi "https://doi.org/10.1016/j.carpath.2013.08.003" @default.
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