Identification and molecular characterization of novel genomic targets in oxidant-induced vascular injury

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Title: Identification and molecular characterization of novel genomic targets in oxidant-induced vascular injury
Author: Partridge, Charles Randal
Abstract: Gene expression was examined in vascular smooth muscle cells to study the complex interaction between oxidative injury and the pathogenesis of vascular disease . Extensive vascular remodeling coupled to increased production of 8 -epi -PGF2 ? ? ? ? nuclear localization of NF ? ? ? ?B , and alterations in glutathione homeostasis were identified as major responses of the vascular wall to oxidative stress . Transcriptional profiling studies , supported by immunohistochemistry and in situ hybridization measurements , identified genes involved in adhesion and extracellular matrix deposition ( ? ? ? ?1 integrin , collagen ) , cytoskeletal rearrangements ( ? ? ? ? -smooth muscle actin , ? ? ? ? -tropomyosin ) , and signal transduction (NF ? ? ? ?B , osteopontin , and LINE ) as targets of oxidant injury . In the case of osteopontin (OPN ) , elevation of OPN levels in vSMCs was shown to be mediated by redox -regulated transcriptional mechanisms . A 200bp region located in the 5' UTR of the osteopontin promoter was found to be responsive to oxidative stress . This regulatory region contained two distinct cis acting elements involved in promoter inducibility . These elements were tentatively identified as NFKB and TIEG -1 binding sites and shown to be highly responsive to hydrogen peroxide and chemical antioxidants . Collectively these studies answer central questions regarding the mechanisms underlying the vascular response to oxidative stress and the involvement of OPN in diseases of the vascular wall .
URI: http : / /hdl .handle .net /1969 .1 /5024
Date: 2007-04-25

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Identification and molecular characterization of novel genomic targets in oxidant-induced vascular injury. Available electronically from http : / /hdl .handle .net /1969 .1 /5024 .

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