PP085. Angiotensin II type 1 receptor antibodies increase angiotensin II sensitivity in pregnant rats.
Pregnancy Hypertens
; 2(3): 286-7, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-26105407
ABSTRACT
INTRODUCTION:
Pregnant women who subsequently develop preeclampsia are highly sensitive to infused angiotensin (Ang) II; the sensitivity persists postpartum. Activating autoantibodies against the Ang II type 1 (AT1) receptor are present in preeclampsia. In vitro and in vivo data suggest that they could be involved in the disease process.OBJECTIVES:
The aim of the study was to show if AT1-AB generated by immunisation alters Ang II sensitivity in pregnant rats.METHODS:
We generated and purified activating antibodies against the AT1 receptor (AT1-AB) by immunizing rabbits against the AFHYESQ epitope of the second extracellular loop, which is the binding epitope of endogenous activating autoantibodies against AT1 from patients with preeclampsia. We then purified AT1-AB using affinity chromatography with the AFHYESQ peptide.RESULTS:
We were able to detect AT1-AB both by ELISA and a functional bioassay. We then passively transferred AT1-AB into pregnant rats, alone or combined with Ang II. AT1-AB activated protein kinase C-alpha and extracellular-related kinase 1/2. Passive transfer of AT1-AB alone or Ang II (435ng/kg per minute) infused alone did not induce a preeclampsia-like syndrome in pregnant rats. However, the combination (AT1-AB plus Ang II) induced hypertension, proteinuria, intrauterine growth retardation, and arteriolosclerosis in the uteroplacental unit. We next performed gene-array profiling of the uteroplacental unit and found that hypoxia-inducible factor 1alpha was upregulated by Ang II plus AT1-AB, which we then confirmed by Western blotting in villous explants. Furthermore, endothelin 1 was upregulated in endothelial cells by Ang II plus AT1-AB. We show that AT1-AB induces Ang II sensitivity.CONCLUSION:
Our mechanistic study supports the existence of an "autoimmune-activating receptor" that could contribute to Ang II sensitivity and possibly to preeclampsia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Pregnancy Hypertens
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha