gms | German Medical Science

Preeclampsia is defined as an increase in blood pressure appearing after 20 weeks gestation accompanied by newly developed proteinuria and commonly edema in a previously normotensive woman. The etiology of preeclampsia remains obscure. We found that women with preeclampsia develop a unique autoantibody directed at the Ang II-Receptor 1 receptor. To elucidate their role in putative mechanisms, we studied the effects of AT1-AA on reactive oxygen species (ROS), NADPH oxidase expression, and nuclear factor-kB (NF-kB) activation in primary human vascular smooth muscle cells (VSMC) and trophoblasts. Angiotensin II (Ang II) and AT1-AA increased ROS production, NADPH oxidase expression and NF-kB activation in both cells. By antisense experiments against p22 phox and VSMC from p47 phox -/- mice, we showed that AngII and AT1-AA induced NF-kB activation is dependent on the NADPH oxidase. We also observed increased ROS generation, NADPH oxidase expression and NF-kB activity and expression in placentas from preeclamptic patients, compared to age-maged healthy controls. In a transgenic rat model, we could show that pregnant female rats transgene for the human angiotensinogen mated with male (transgenic for human rennin) develop hypertension in the last term of pregnancy and proteinuria. They also devolp AT1-AA. The opposite cross (female: human Renin) x father (human angiotensinogen) does not develop the described clinical features.

AT1-AA might account for the well-established production of ROS and inflammatory responses in preeclampsia via activation of the NADPH oxidase could account. We suggest that we have established an animal model for preeclampsia, where AT1-AA can be detected.