Abstract 15328: Decreased Aldosterone in Preeclampsia Patients: Role of Autoantibodies Against the Second Extracellular Loop of Angiotensin II Type I Receptor
Impaired aldosterone (ALD) generation is involved in the pathogenesis of preeclampsia (PE) where angiotensin II type 1 receptor agonistic autoantibody (AT1-AA) pathologically activates AT1 receptor as a functional receptor agonist. However, the mechanistic correlation of AT1-AA with ALD underlying PE remains unknown.. We therefore detected circulating AT1-AA and ALD levels of 76 patients with PE (35 severe and 41 mild), 26 patients with gestational hypertension (GH), and 50 normotensive healthy pregnancies. We found that women with early-onset PE had higher AT1-AA levels than those with late-onset PE (0.703 ± 0.132 vs. 0.567 ± 0.111, P < 0.01), and AT1-AA may be predictive of severe PE among those hypertensive pregnant women before the clinical manifestation of PE (AUC = 0.870 vs. 0.5, P < 0.001; Youden Index= 0.7115). A lower ALD level was found in AT1-AA-positive than in AT1-AA-negative PE patients (0.257 ± 0.075 vs. 0.296 ± 0.076 ng/ml, P 5.0 g/24h), AT1-AA and ALD showed an inverse correlation (r = -0.573, P < 0.001). Next, we observed that injection of purified AT1-AA from preeclamptic women into pregnant rats reduced ALD from 0.345 ± 0.07 to 0.2031 ± 0.0887 ng/ml (P < 0.05). Chronic administration of rat AT1-AA into normal nonpregnant rats induced ALD concentrations from 0.273 ± 0.03 to 0.123 ± 0.08 ng/ml (P < 0.05) and marked impairment of adrenal cortical zona. Cessation of AT1-AA administration corrected ALD levels. Finally, we found that the short-term presence of lower-level AT1-AA enhanced the proliferation of NCI-H295R human adrenal gland carcinoma cells, and ALD production. However, the long incubation of AT1-AA inhibited cellular growth characterized by increased necrosis and apotosis in a concentration-dependent manner. These effects could be blocked by the selective AT1 recetptor antagonist losartan. Overall, these data reveal that AT1-AA, highly prevalent in early-onset PE patients, negatively correlates with ALD levels. Furthermore, Long-term existence of AT1-AA reduces ALD in a pregnancy-independent manner.
- © 2013 by American Heart Association, Inc.