Maternal autoantibodies from preeclamptic @entity1 activate angiotensin receptors on XXXX trophoblast cells.

@entity1 @entity2289 @entity535 @entity9886 @entity205 @entity1468 @entity460 @entity35 @entity7743
OBJECTIVES: Recent evidence indicates that @entity1468 is associated with the presence of autoantibodies capable of activating the angiotensin II receptor, @entity7743 . We sought to evaluate the role of @entity7743 agonistic autoantibodies ( @entity7743 -AA) in two major features of @entity1468 -increased @entity2289 ( @entity2289 ) production and shallow trophoblast invasion. METHODS: This study included 38 pregnant @entity1 , 20 of whom had severe @entity1468 and 18 normotensive individuals. Immunoglobulin (Ig)G was purified from these individuals, and the presence of @entity7743 -AA was determined based on its ability to stimulate an increase in the contraction rate of cultured @entity35 neonatal cardiac myocytes. Immortalized @entity1 trophoblasts were chosen to study @entity2289 production and secretion after treatment with IgG from normotensive and preeclamptic @entity1 . An in vitro Matrigel invasion assay was used to test the effect of @entity7743 -AA on the invasive properties of @entity1 trophoblasts. @entity9886 and @entity205 were used to determine whether the @entity7743 -AA-induced stimulation of @entity2289 secretion is through the @entity7743 receptor and the calcineurin-nuclear factor of activated t-cells (NFAT)-dependent pathway. RESULTS: The results show that IgG from 18 of 20 severely preeclamptic @entity1 stimulated increased cardiomyocyte contraction rates of 20-40 beats per minute. A significant stimulation of @entity2289 secretion from @entity1 trophoblasts was observed with IgG from the same 18 of 20 @entity1 with severe @entity1468 . Of IgG obtained from 18 normotensive pregnant @entity1 , only two showed a relatively low level of biologic activity in the cardiomyocyte contraction and @entity2289 secretion assays. Activation of @entity7743 receptors by @entity7743 -AA was blocked by @entity9886 (an @entity7743 receptor antagonist) and by a seven @entity535 peptide corresponding to a sequence present on the second extracellular loop of the @entity7743 receptor. Activation of @entity7743 receptors by @entity7743 -AA resulted in decreased trophoblast invasiveness as determined by the in vitro Matrigel invasion assay. Additional data indicate that @entity7743 receptor activation by @entity7743 -AA is followed by the downstream activation of the @entity460 -dependent calcineurin-NFAT signaling pathway leading to increased @entity2289 gene expression. CONCLUSION: Our findings suggest that maternal autoantibody with the ability to activate @entity7743 receptors may account for two features of @entity1468 , increased @entity2289 production and shallow trophoblast invasion.
