• 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

    The Roles of Circadian Disruption and Reactive Oxygen Species Overproduction in the Development of Obesity-Associated Cardiovascular Disease

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Padgett_gru_1907E_10266.pdf
    Size:
    2.920Mb
    Format:
    PDF
    Download
    Authors
    Padgett, Caleb
    Issue Date
    2022-07-13
    URI
    http://hdl.handle.net/10675.2/624344
    
    Metadata
    Show full item record
    Abstract
    Obesity is a complex and multifactorial disease that is endemic in the United States, affecting over 40% of the US population and contributing to over $150 billion in medical cost. Obesity and metabolic disease are major risk factors for cardiovascular disease, which is the leading cause of death among Americans, especially those in the southeast. While the detrimental effects of obesity on cardiovascular health are well-documented, the mechanisms linking aberrant metabolism to vascular dysfunction are poorly understood. In the present study, we investigate the role of the vascular endothelium in mediating the progression of cardiometabolic disease through disruption of the peripheral circadian clock as well as through overproduction of reactive oxygen species, both of which are implicated in the development of endothelial dysfunction and the downstream acute cardiovascular diseases it predicts. We demonstrate that obesity causes a unique circadian disruption in the endothelium that is not recapitulated by other established models of circadian disruption, and that rhythmic expression of the essential vasodilatory enzyme endothelial nitric oxide synthase (eNOS) is disturbed. Expression of NADPH oxidase I (NOX1), the major pathological reactive oxygen species (ROS)-producing enzyme in the vasculature, was markedly increased in the endothelium, and was found to be even more highly expressed in the obese microvascular endothelium. Further, endothelial expression of the receptor for glycation end-products galectin-3 (GAL3) was found to correlate with NOX1 expression levels, leading us to hypothesize that GAL3 contributes to obesity-induced NOX1 overexpression in the microvascular endothelium. We demonstrate that deletion of GAL3 resolves obesity-induced endothelial dysfunction and hypertension by decreasing NOX1 expression and subsequent ROS overproduction. Finally, we demonstrate that the GAL3/NOX1 axis is amenable to beneficial changes in glucose handling by treatment with metformin, augmentation of skeletal muscle mass, or improvement of insulin signaling. Taken together, these data indicate that GAL3 is an attractive therapeutic target to ameliorate obesity-induced cardiovascular disease.
    Affiliation
    Biomedical Sciences
    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.