On the Role of The (Pro)Renin-Angiotensin System in Preeclampsia

Preeclampsia is a disorder of gestation characterized by hypertension and
proteinuria and an important cause of maternal and neonatal morbidity and
mortality. The cause of preeclampsia is unknown but several lines of evidence
indicate involvement of the renin-angiotensin system (RAS). In preeclampsia the
vasoconstrictor sensitivity of resistance arteries to angiotensin II is
increased. In amniotic fluid high concentrations of prorenin, the precursor of
renin, have been reported. Mating of transgenic female mice or rats with
overexpression of human angiotensinogen with transgenic male mice or rats with
overexpression of renin leads to preeclampsia-like syndrome in pregnant
animals. In women with preeclampsia antibodies that are agonistic for the
angiotensin II, subtype 1 receptor have been reported. Finally in subjects with
diabetes mellitus the concentration of prorenine is increased and this
increased concentration is a predictor of and associated with microvascular
disease.
One hypothesis is that in preeclampsia the local placental RAS is activated,
and that this local activated system influences the maternal circulating RAS.
This could explain why the circulating RAS is less active in preeclampsia than
it is in normal pregnancy.

The primary objective of our study is get more insight in the role of the RAS
in preeclampsia. For this purpose concentrations of RAS components in the
maternal circulation and amniotic fluid and the expression of RAS genes in the
maternal and foetal part of the placenta are measured. In resistance vessels,
isolated from subcutaneous fat biopsies, the change in function of the
angiotensin II, type receptor during normotensive pregnancy and preeclampsia is
evaluated and in a human endometrial cell-line the function of the recently
discovered (pro)renin-receptor is evaluated.

For this study blood, amniotic fluid, placental tissue and abdominal
subcutaneous fat tissue for isolation of resistance arteries is sampled from
healthy and preeclamptic women who are subjected to a caesarian section. The
above mentioned material is also sampled from pregnant women with diabetes
mellitus with or without preeclampsia who are subjected to a caesarian section.
In non-pregnant women < 50 years who undergo and abdominal gynaecological
operation blood and subcutaneous fat tissue is sampled as well.
Different methods, ranging from functional vessel research, gene expression and
biochemical measurements will be appied to address the objectives.

The burden to participate in this study is minimal. Participation will extend
the surgical procedure by maximal 5 minutes. Participation in this study is not
associated with risks.