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- Title
AT1-Receptor Autoantibodies in a Transgenic Animal Model for Preeclampsia.
- Authors
Muller, N.; Dechend, R.; Shagdarsuren, E.; Gratze, P.; Bräsen, J. -H.; Park, J. K.; Fiebeler, A.; Wallukat, G.; Luyten, C.; Pijnenborg, R.; Luft, F. C.
- Abstract
Objective: We previously described activating autoantibodies against the Angiotensin 1 Receptor (AT1-AA) in patients with preeclampisa that are not present in patients with normal pregnancy. We showed earlier that female rats transgenic for human angiotensinogen mated with rats transgenic for human renin develop gestational hypertension. We relied on this model to search for AT1-AA with a beating neonatal rat cardiomyocyte bioassay. Results: Telemetry BP increased in the third trimester of pregnancy (day 14) from 105/80mmHg to as high as 170/140mmHg and returned to normal after delivery. Echocardiographic dp/dt was also increased. The opposite cross and Sprague Dawley dams mated with sires transgenic for human renin had normal blood pressures throughout pregnancy. Proteinuria was increased from 0.1 mg/dl in the two control groups to 8.2 mg/dl in the hypertensive group. Further, macrophage and T lymphocytes were significantly increased, compared to controls. Renal immunohistochemistry showed glomerular pathology with increased fibrin expression, C1q and C3 complement fractions, and IgG. Although overall interstitial and endovascular trophoblast invasion was normal in both decidua and mesometrial triangle, branches of spiral arteries in the latter compartment occasionally showed atherosis with presence of trophoblastic remnants and inflammatory cells in the necrotic vessel walls. AT1-AA were not detected before the pregnancy. However, by day 18 of pregnancy, the AT1-AA assay was positive. Conclusions: We present a rat model of preeclampsia that features hypertension, proteinuria, and AT1-AA. This model should greatly facilitate investigations regarding the pathogenic significance of AT1-AA.
- Subjects
AUTOANTIBODIES; ANGIOTENSINS; PREECLAMPSIA; PREGNANCY; RATS
- Publication
Kidney & Blood Pressure Research, 2004, Vol 27, Issue 5/6, p299
- ISSN
1420-4096
- Publication type
Article