P290	Accelerated arteriolosclerosis in a transgenic rat model of preeclampsia.
1P.Gratze, 1E.Shagdarsuren, 1A.Fiebeler, 3R.Pijnenborg, 2G.Wallukat, 1F.C.Luft, 1D.N.Mueller, 1R.Dechend
1HELIOS Klinik, Charite, Campus-Buch, Berlin, DE; 2Max-Delbrueck Zentrum, Berlin, DE; 3Experimenteel Laboratorium Gynecologie, Universitair Ziekenhuis Gasthuisberg, Leuven, BE.

We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen x male hRen cross-developed severe hypertension and albuminuria during the last trimester of pregnancy that subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not. Telemetry blood pressure increased in the third trimester of pregnancy (day 14) from 105/80 mmHg to as high as 170/140 mmHg and returned to normal after delivery. We demonstrated that the female hAogen x male hRen cross developed agonistic antibodies capable of activating the angiotensin (Ang) II AT1 receptor (AT1R-AA) and defined the epitope on the receptors second extracellular loop. The phenomenon also described in humans with preeclampsia. Further, macrophage and T lymphocytes were significantly increased, compared to controls. Renal immunohistochemistry showed vascular and glomerular pathology with increased fibrin expression, C1q and C3 complement fractions, and IgG. The spiral arteries in the placenta bed featured acute arteriolosclerosis. Vascular remodeling and trophoblast invasion was failed in these vessels. Our model may have utility in elucidating vascular remodeling in normal placenta and preeclampsia (accelerated arteriolosclerosis). We wil also investigate the pathogenic significance of AT1-AA.

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