From microenvironment to epigenetics in endothelial cells

Monika Maleszewska

    Research output: ThesisThesis fully internal (DIV)

    2315 Downloads (Pure)

    Abstract

    Endothelial cells line all blood vessels of the body and are necessary for the cardiovascular system to work properly. When endothelial cells lose their functionality, it can lead to serious complications, such as cardiovascular disease.
    The organs in the body serve different functions, thus endothelial cells are exposed to different surroundings in different organs. Although we call them all ‘endothelial cells’, they are in fact different in different parts of the body. To function properly endothelial cells are plastic and adjust their appearance and behavior to the local demands. These local demands invoke specific biochemical and mechanical signals in endothelial cells, which are transmitted inside the cell to the genetic material. This causes changes that make parts of the genetic material available or unavailable. These are called epigenetic changes. Epigenetic changes shape the appearance and behavior of cells. However, we know little about how endothelial cells transmit the information from their surroundings to the epigenetic level.
    In this thesis we investigated how different factors in the surrounding of endothelial cells, in particular blood flow and inflammation, work together to change their behavior. We identified an epigenetic factor called EZH2, is regulated by these different microenvironmental signals in endothelial cells. We showed that EZH2 affects many genes in endothelial cells, especially genes that drive cell divisions. Our findings suggest that low levels of EZH2 keep the cells in a protected, resting state, characteristic for healthy blood vessels. In the future, EZH2 could maybe become a new target to prevent cardiovascular disease.
    Translated title of the contributionVan micro-omgeving te epigenetica in endotheelcellen
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Harmsen, Marco, Supervisor
    • Krenning, Guido, Co-supervisor
    Award date15-Apr-2015
    Place of Publication[groningen]
    Publisher
    Print ISBNs978-94-6259-602-3
    Electronic ISBNs978-94-6259-603-0
    DOIs
    Publication statusPublished - 2015

    Cite this