Microvascular endothelial responses in critical illness: Focus on the Ang/Tie2 system

    Research output: ThesisThesis fully internal (DIV)

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    Critically ill patients in the Intensive Care unit need medical care, because of failure of one or more organs. These patients suffer from systemic low blood pressure, caused by alterations in blood flow in the smallest blood vessels. As a consequence the organs are ‘leaky’, leading to edema formation. This can result in organ failure or even death. The cause for these leaky blood vessels in critically ill patients is not known. The aim of the research described in this thesis was to study the behavior of the endothelial cells in blood vessel wall of critically ill patients and in models thereof. We showed that in blood of patients who underwent cardiac surgery the balance of the molecules of the Angiopoietin/Tie2 system, the system that regulates the integrity of blood vessels, is disturbed. This balance in soluble Ang/Tie2 molecules is more deranged in these patients who developed kidney failure after cardiac surgery. Furthermore, in kidneys of patients who died of sepsis-induced acute kidney injury, the Tie2 production is diminished. In cell models, we demonstrated that this loss of Tie2 can be a result of a decrease in shear stress which reflects a reduction in blood flow in vivo. In mouse models mimicking critical illness, the inflammatory responses of the endothelium are not changed when the expression of Tie2 is halved by genetic manipulation. Future research will focus on unraveling the underlying mechanisms of the endothelial Ang/Tie2 system in blood vessels in critical illness.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Molema, Ingrid, Supervisor
    • Zijlstra, Jan, Supervisor
    • Struys, Michel, Supervisor
    • van Meurs, Matijs, Co-supervisor
    Award date1-Nov-2017
    Place of Publication[Groningen]
    Print ISBNs978-94-034-0104-1
    Electronic ISBNs978-94-034-0103-4
    Publication statusPublished - 2017

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