Hydrogen sulfide in preeclampsia
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 has shown 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. We did show 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 is a potential target for treatment of hypertension and proteinuria in women with PE.