Abstract P090: The Contractile Effect of Angiotensin II Type 1 Receptor Autoantibodies on Human Placental Vessels

Abstract

Background: Decreased placental perfusion induced by abnormal placental vascular contraction is one of the pathological basis of preeclampsia. It has been reported that the sera titers of the autoantibody against the second extracellular loop of angiotensin II type 1 receptor (AT1-AA) were negatively correlated with placental blood flow in preeclampsia. Our previous study has found that AT1-AA could induce contraction of rat thoracic aorta and coronary rings by activing angiotensin II type 1 receptor (AT1R). However, there is no direct evidence for explaining whether AT1-AA might cause vasoconstriction on human placental blood vessels. Methods: The SD rats were immunized with the synthetic peptide corresponding to the sequence of the second extracellular loop of the human AT1 receptor (AT1R-EC II ), and anti-AT1R antibody (AT1R-Ab) was extracted. The expression of AT1R on human placental vessels was determined by immunohistochemistry. The effects of AT1R-Ab on placental vessels were measured with isolated vascular ring technique. Results: (1) AT1R was highly expressed in the human placental artery, vein and vascular endothelial cells. (2) AT1R-Ab (10 mmol/L) respectively enhanced the contraction of the placental arteries and veins (29.21% ± 3.7% vs . 21.35% ± 2.8%, P >0.05), which could be completely reversed when AT1R was blocked by AT1R inhibitor. (3) AT1R-Ab (0.1, 1 and 10 mmol/L) induced placental vasoconstriction of normal human. The percentage of maximal contraction was 2.73% ± 1.11%, 4.00% ± 3.2% and 33.30% ± 5.6%, respectively. There was significantly difference between the three groups for contraction amplitude induced by different concentrations of AT1R-Ab ( P <0.01). (4) AT1R-Ab (0.1, 1 and 10 mmol/L) induced placental vasoconstriction of preeclampsia. The percentage of maximal contraction was 1.74% ± 0.3%, 5.58% ± 1.41% and 3.73% ± 2.5%, respectively. There was significantly difference between the three groups for contraction amplitude induced by different concentrations of AT1R-Ab ( P <0.01). Conclusion: AT1R-Ab could induce human placental vasoconstriction in a concentration-dependent manner, which suggested that AT1-AA might be involved in the pathogenesis of preeclampsia by directly contracted placental blood vessles.