Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.
The renin-angiotensin system (RAS) participates in preeclampsia; however, the relative contributions from the circulating RAS and the tissue-based, uteroplacental RAS are unknown. We hypothesized that the tissue-based uteroplacental RAS is dysregulated in preeclampsia. We performed microarray and gene expression studies and confirmed the findings on the protein level by immunohistochemistry in ureteroplacental units from 10 preeclamptic women and 10 women with uneventful pregnancies. All of the women were delivered by cesarean section. We also analyzed plasma renin activity and circulating agonistic angiotensin II type 1 (AT1) receptor autoantibodies. In preeclampsia, we found that the angiotensin II AT1 receptor gene was 5-fold upregulated in decidua (maternal origin). We also found AT1 autoantibodies in preeclamptic women and in their offspring by neonatal cardiomyocyte bioassay compared with women with normal pregnancies and their infants (mother: 17.5+/-2.2 versus 0.05+/-0.4; fetus: 14.5+/-1.8 versus 0.5+/-0.5 Deltabpm). Gene expressions for renin (35.0-fold), angiotensin-converting enzyme (2.9-fold), and angiotensinogen (8.9-fold) were higher in decidua than placenta (fetal origin) in both control and preeclamptic women, whereas the AT1 receptor was expressed 10-fold higher in placenta than in decidua in both groups. Our findings elucidate the ureteroplacental unit RAS in preeclamptic and normal pregnancies. We found that, in preeclampsia, the AT1 receptor expression is particularly high in decidua, combined with pregnancy-specific tissue RAS involving decidual angiotensin II production and AT1 autoantibodies. We also showed that AT1 autoantibodies cross the ureteroplacental barrier. These components could participate in the pathophysiology of preeclampsia.
Herse
Florian
F
Medical Faculty of the Charité, Franz-Volhard Clinic, HELIOS Klinikum, Berlin, Germany.
Dechend
Ralf
R
Harsem
Nina K
NK
Wallukat
Gerd
G
Janke
Jürgen
J
Qadri
Fatimunnisa
F
Hering
Lydia
L
Muller
Dominik N
DN
Luft
Friedrich C
FC
Staff
Anne C
AC
D000328:Adult; D000809:Angiotensins / Q000032:analysis / Q000096:biosynthesis; D001323:Autoantibodies; D003656:Decidua / Q000737:chemistry / Q000503:physiopathology; D005260:Female; D006801:Humans; D010920:Placenta / Q000737:chemistry / Q000503:physiopathology; D021041:Placental Circulation; D011225:Pre-Eclampsia / Q000235:genetics / Q000503:physiopathology*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000276:immunology; D012083:Renin / Q000032:analysis / Q000096:biosynthesis; D012084:Renin-Angiotensin System / Q000502:physiology*
D000809:Angiotensins; D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D012083:Renin