Abstract 2517: Presence of Auto-antibody against Angiotensin II Receptor in Pregnant Women and Its Potential Role in the Development of Preeclampsia
Preeclampsia is a serious pathologic complication during pregnancy but its pathogenesis remains unclear. We recently demonstrated that production of auto-antibody against angio-tensin (AGN) II type I receptor (AT1-AA) causes hypertension in experimental animals. Current study determined whether AT1-AA is present in pregnant women and if so, to investigate its potential role in the development of preeclampsia. Blood samples were collected from 35 pregnant women (preeclampsia=18, control=17) and AT1-AA was detected. To determine the potential mechanisms by which AT1-AA may contribute to the development of preeclampsia, vasoconstrictive effects of purified AT1-AA was determined in isolated rat arteriae cerebri media and its pro-apoptotic and cytotoxic effect was determined in cultured HUVEC. Compared with the normal pregnant women (week 37 to 39), sera levels of AT1-AA were markedly increased in preeclamptic patients (0.27±0.03 μmol/L vs. 0.023±0.017 μmol/L, P<0.01). In isolated resistant vascular rings, AT1-AA at pathologically relevant concentrations (0.1 to 0.5 μmol/L) caused significant vasoconstriction (P<0.01) which was completely blocked by losartan, an AT1-receptor antagonist. These results demonstrated that the AT1-AA causes vascular constriction though activation of AT1-receptor. Moreover, in vitro incubation of HUVEC with AT1-AA (0.5 μmol/L, 48 hours) resulted in significant caspase activation (caspase-3 and caspase-8: 0.69±0.14 and 3.54±0.24 nmol/h/mg protein with AT1-AA vs. 0.02±0.02 and 0.95±.28 nmol/h/mg protein with normal sera, P<0.01) and a >2-fold increase in LDH release (P<0.01). The pro-apoptotic and cytotoxic effect of AT1-AA was almost identical with that seen in AGN II-treated HUVEC. Collectively, current study demonstrated that AT1-AA is markedly increased in preeclamptic patients. More importantly, purified AT1-AA not only has a direct vasoconstrictive effect which increases blood pressure, but also causes significant endothelial cell death that indirectly contributes to the development of hypertension. These results suggest that production of AT1-AA is a novel risk factor in pregnant women and this auto-antibody may play a causative role in the development of preeclampsia.