Hydrogen Sulfide in Preeclampsia: Potential Therapeutic Implications

Kim Holwerda

    Research output: ThesisThesis fully internal (DIV)

    2312 Downloads (Pure)


    The thesis provide insights into the production and possible therapeutic effect of the gaseous molecule hydrogen sulfide (H2S) in preeclampsia (PE). H2S is an important molecule in the (human) body. It is among others involved in blood pressure regulation, stimulation of vascular growth and modulation of the immune system. The production of H2S is impaired in several diseases, such as cardiovascular disease. In animal models for cardiovascular disease, H2S therapy have been shown to have beneficial effects. PE is a pregnancy related syndrome, characterized by high blood pressure (hypertension) of the mother and protein excretion by the kidneys in the urine (proteinuria). Until now, no effective therapy for PE is available. We hypothesize that H2S is involved in the development of PE and that H2S has therapeutic potential for the disease.
    In the thesis, we demonstrate the presence of the two H2S producing enzymes (CBS and CSE) in the human placenta. We demonstrated that the production of one of these enzymes (CBS) is impaired in placentas from women with PE. Moreover we showed that a genetic mutation in the CBS gene is associated with a reduced risk for PE.
    In a non-pregnant rat model with hypertension and proteinuria we evaluated the therapeutic effect of H2S and revealed that H2S therapy reduced both blood pressure and proteinuria. However, in a pregnant rat model we were not able to induce hypertension and proteinuria and therefore we could not assess the effect of H2S therapy in pregnant rats. However, we showed that H2S therapy reduced the sensitivity of vessels to contract.
    The overall conclusion of the thesis is that H2S might play a role in the development of PE and that H2S therapy has the potential to target hypertension and proteinuria in women with PE.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • van Goor, Harry, Supervisor
    • Lely, Anna, Co-supervisor
    • Faas, Marijke, Co-supervisor
    Award date30-Nov-2015
    Place of Publication[Groningen]
    Print ISBNs978-94-92332-01-1
    Electronic ISBNs978-94-92332-02-8
    Publication statusPublished - 2015


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