PubMed:15797649
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15797649","sourcedb":"PubMed","sourceid":"15797649","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15797649","text":"Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion.\nBACKGROUND: Preeclampsia affects 3-5% of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Recent studies demonstrate that autoantibodies against the angiotensin II type 1 (AT(1)) receptor are present in the serum of preeclamptic patients. In this study, we investigated the role of AT(1) receptor-agonistic autoantibody (AT1-AA) regarding interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (Pai-1) secretion in human mesangial cells.\nMETHODS: The study included ten patients: five severely preeclamptic and five normotensive pregnant women. Immunoglobulin-G (IgG) was purified from each individual. The presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of rat neonatal cardiomyocytes. Primary human mesangial cells were chosen to study IgG-induced secretion of IL-6 and Pai-1. Losartan and epitope peptides were used to determine whether AT1-AA interaction with AT(1) receptor was associated with stimulation of IL-6 and Pai-1 secretion and was mediated through AT(1) receptor activation.\nRESULTS: The IgG from preeclamptic patients stimulated an increased contraction rate in rat neonatal cardiomyocytes. The IgG from preeclamptic patients induced the AT(1) receptor-specific secretion of IL-6 and Pai-1 from human mesangial cells at a significantly higher level than that achieved with IgG from normotensive patients. Competition with an epitope peptide suggested that the AT(1) receptor was stimulated by AT1-AA.\nCONCLUSIONS: Our findings suggest that a maternal autoantibody with the ability to activate AT(1) receptors may account for the development of renal damage seen in preeclamptic 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