Angiotension Ⅱ Type 1 Receptor Autoantibody as A Novel Negative Regulator of Aldosterone in Preeclam

• 作 者: Jie Yang Xin-Liang Ma Hui-Rong Liu Li Li Jian-Yu Shang Lin Cai Song Li Su-Li Zhang Hao Li Xiao Li Wayne Bond Lau
• 机 构: Department of Physiology & Pathophysiology, Capital Medical University, Beijing, China
• 出 处: 首都医科大学2013年研究生学术论坛
• 发表日期: 2013年2期

　　Objectives This study investigated the correlation between changes in angiotensin Ⅱ type 1 receptor agonistic autoantibody (AT1AA) and aldosterone (ALD) in preeclampsia (PE).Background Impaired ALD generation is involved in the pathogenesis of PE, where AT1AA pathologically activates AT1 receptor as a functional receptor agonist.High AT1AA levels have recently been detected in primary aldosteronism.However, whether AT1AA and ALD levels have any mechanistic relationship underlying preeclampsia remains unknown.Methods Circulating titers of AT1AA and ALD of 76 patients with PE (35 with severe PE, 41 with mild PE), 26 patients with gestational hypertension (GH), and 50 normotensive healthy pregnancies were measured.Purified AT1AA from both preeclamptic patients and passively-immunized rats was injected into pregnant and nonpregnant rats respectively at a clinically-relevant dose.Results Women with early-onset PE had increased AT1AA levels than those with late-onset PE (0.703 ± 0.132 vs 0.567 ± 0.111, P < 0.01).AT1AA-positive patients had decreased circulating ALD levels (0.257 ± 0.075 vs 0.296 ± 0.076 ng/ml, P < 0.05).Among patients with early-onset PE characterized by high proteinuria (> 5.0 g/24h), AT1AA and ALD showed inverse correlation (r =-0.573, P < 0.001).Injection of AT1AA into pregnant rats reduced ALD (from 0.345 ± 0.07 to 0.2031 ± 0.0887 ng/ml, p < 0.05).Chronic administration of AT1AA in nonpregnant rats decreased ALD (from 0.273 ± 0.03 to 0.123 ± 0.08 ng/ml, P < 0.05).Cessation of AT1AA administration corrected ALD levels.