Thrombin and Nad(P)h Oxidase-mediated Regulation of Cd44 and Bmp4-id Pathway in Vsmc, Restenosis, and Atherosclerosis.
From: Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7055, USA.
Circulation research
- Publish Date: May 2006
- ISSN: 1524-4571
- Volume: 98
- Issue: 10
- Pages: 1254-63
- Medium: Internet
- Language: English
- Citation (JAMA): Vendrov Aleksandr E, Madamanchi Nageswara R, Hakim Zeenat S, et al. Thrombin and Nad(P)h Oxidase-mediated Regulation of Cd44 and Bmp4-id Pathway in Vsmc, Restenosis, and Atherosclerosis.. Circ. Res. May 2006;98:1254-63
Abstract
To characterize novel signaling pathways that underlie NAD(P)H oxidase-mediated signaling in atherosclerosis, we first examined differences in thrombin-induced gene expression between wild-type and p47phox(-/-) (NAD[P]H oxidase-deficient) VSMC. Of the 9000 genes analyzed by cDNA microarray method at the G1/S transition point, 76 genes were similarly and significantly modulated in both the cell types, whereas another 22 genes that encompass various functional groups were regulated in NAD(P)H oxidase-dependent manner. Among these 22 genes, thrombin-induced NAD(P)H oxidase-mediated regulation of Klf15, Igbp1, Ak4, Adamts5, Ech1, Serp1, Sec61a2, Aox1, Aoh1, Fxyd5, Rai14, and Serpinh1 was shown for the first time in VSMC. The role of NAD(P)H oxidase in the regulation of a subset of these genes (CD44, BMP4, Id1, and Id3) was confirmed using modulators of reactive oxygen species (ROS) generation, a ROS scavenger and in gain-of-function experiments. We then characterized regulation of these genes in restenosis and atherosclerosis. In both apoE(-/-) mice and in a mouse vascular injury model, these genes are regulated in NAD(P)H oxidase-dependent manner during vascular lesion formation. Based on these findings, we propose that NAD(P)H oxidase-dependent gene expression in general, and the CD44 and BMP4-Id signaling pathway in particular, is important in restenosis and atherosclerosis.
Mesh Headings (Keywords): Animals, Antigens, CD44, Aorta, Atherosclerosis, Bone Morphogenetic Proteins, Cells, Cultured, Constriction, Pathologic, Femoral Artery, Gene Expression Regulation, Hyperplasia, Inhibitor of Differentiation Protein 1, Inhibitor of Differentiation Proteins, Mice, Mice, Knockout, Muscle, Smooth, Vascular, NADPH Oxidase, Oxidation-Reduction, Reactive Oxygen Species, Thrombin, Tunica Intima, Wounds and Injuries
Check for Full Text / PubMed Unique Identifier (PMID): 16601225
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