Identification of a novel agonist-like autoantibody in preeclamptic patients.
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Data
2016
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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.
Descrição
Palavras-chave
Blood pressure, Endothelin, Hypertension, Preemclampsia
Citação
VELLOSO, E. P. et al. Identification of a novel agonist-like autoantibody in preeclamptic patients. American Journal of Hypertension, v. 29, p. 405-412, 2016. Disponível em: <https://academic.oup.com/ajh/article-lookup/doi/10.1093/ajh/hpv099>. Acesso em: 29 ago. 2017.