ABSTRACT
BACKGROUND: Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of PE. METHODS: To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists. RESULTS: Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype. CONCLUSIONS: We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE.
Subject(s)
Autoantibodies/pharmacology , Heart Rate/drug effects , Myocytes, Cardiac/drug effects , Pre-Eclampsia/immunology , Protein Kinase C/drug effects , Receptor, Angiotensin, Type 1/drug effects , Receptor, Endothelin A/drug effects , Adult , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Autoantibodies/immunology , Biphenyl Compounds/pharmacology , Case-Control Studies , Endothelin Receptor Antagonists/pharmacology , Enzyme Inhibitors/pharmacology , Female , Gestational Age , Humans , Irbesartan , Naphthalenes/pharmacology , Peptides, Cyclic/pharmacology , Pregnancy , Pregnancy Trimester, Third , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/immunology , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/immunology , Receptor, Endothelin A/immunology , Severity of Illness Index , Tetrazoles/pharmacology , Young AdultABSTRACT
Heart auscultation remains as an important clinical tool in heart disease diagnostics. A prototype was developed, using an existing database of clinical and cardiac sounds of pregnant women [1]. The context for virtual learning is cardiac disease during pregnancy (Partum and Post Partum situations). Based on real histories, cardiac sounds, and complementary exams, this pilot presents the most frequent diagnosis of cardiac diseases during pregnancy.
