• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarly CommonsCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    About

    AboutCreative CommonsAugusta University LibrariesUSG Copyright Policy

    Statistics

    Display statistics

    Angiotensin II signaling mechanisms involved in the elevation of arginase activity/expression and vascular dysfunction

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Shatanawi_Alia_PhD_2011.pdf
    Size:
    7.595Mb
    Format:
    PDF
    Download
    Authors
    Shatanawi, Alia
    Issue Date
    2011-11
    URI

    http://hdl.handle.net/10675.2/623386
    
    Metadata
    Show full item record
    Abstract
    Vascular endothelial dysfunction is a major cause of morbidity and mortality in · patients with cardiovascular diseases such as hypertension, atherosclerosis and diabetes. Nitric oxide (NO) produced by endothelial nitric oxide synthase (NOS) is· needed for norm.al vascular function. During hypertension, diabetes or -atherosclerosis, elevated levels of arginase can compete with NOS for available L-arginine thus reducing vascular NO production. Elevated angiotensin II (Ang II) is a key participant of endothelial dysfunction in many cardiovascular diseases and has been linked to elevated arginase activity. In this· study we explored the signaling pathway leading to increased arginase expression/activity in responses to Ang II.in bovine aortic endothelial cells (BAEC). Treatment of BAEC with Ang II (10-7 _M, 24 hrs) caused a 40±6% increase in arginase activity. This was accompanied by 30±8% decrease in NO production. Our studies indicate involvement of the RhoA/ROCK-p38 mitogen activated protein kinase (MAPK) in Ang 11.,induced arginase upregulation and reduced NO production, as inhibitors of ROCK or p38 MAPK prevented the Ang II-induced increase in arginase activity. Our studies in mice also show involvement of p38 MAPK in Ang II-induced vascular dysfunction associated with elevated arginase activity and expression. Ang 11 (42 · μg/kg/h) caused impaired EC-dependeht vasorelaxation in mouse . aorta (55±7~ vs. -75±8% for control}. This ·impairment was prevented by treatment with p38 inhibitor S8203580. (5 μg/kg/day). Ang II also caused a 6.2 fold increase in vascular arginase activity/expression that was complete_ly prevented by p38 MAPK inhibition. Additionally, treatment of BAEC with Ang II causes phosphorylation of activating transcription factor-2 (ATF-2) and -enhancement of the binding of ATF-2 to arginase promoter through an AP-1 site . as evident from electrophoretic mobility shift assay experiments. Transfection of BAEC with ATF-2 siRNA prevents Ang II-induced increases in arginase activity/expression and maintains NO production. These results indicate that. ATF-2 is necessary for enhanced expression of arginase by Ang II. Collectively, our results indicate that Ang 11 increases endothelial arginase activity/expression through a RhoA/ROCK-p38 MAPK-ATF-2 pathway leading to reduced NO production and endothelial dysfunction. Targeting these signaling steps might be therapeutic points for preventing vascular endothelial dysfunction_ associated with · elevated arginase activity/expression.
    Affiliation
    School of Graduate Studies
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.