Proteinuria and Elevated sPRR Are Associated With PreEclampsia in African Green Monkeys
Authors: Dixit Sushovan , Weaver Chelsea , Gatineau Eva , Poupeau Audrey , Osborn Jeffrey , Yiannikouris Frederique 
Published: April 2020

Disorders related to gestational hypertension, such as preeclampsia (PE), are the leading cause of maternal and fetal mortality worldwide. PE can increase the risk of hypertension (HTN) and cardiovascular disease later in the life of the offspring and mother. PE is a complex pathology that can be affected by numerous mechanisms, including the renin‐angiotensin‐aldosterone‐system (RAAS). The soluble prorenin receptor (sPRR) is a newly identified component of RAAS that may be implicated in the onset of PE. sPRR is a circulating form of the prorenin receptor that could be a biomarker for increased blood pressure (BP) in pregnancy. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus) is a novel, nonhuman primate that develops spontaneous hypertension, as well as PE in previously normotensive females. We hypothesize that plasma sPRR concentrations are associated with the pathogenesis of PE. Pregnant and nonpregnant female AGMs were singly housed for 1 week for the collection of plasma, urine output and water intake. Samples were collected before (NP PE) and during pregnancy (P PE) for animals who ultimately developed PE. Systolic blood pressures (SBP) were measured using forearm plethysmography before, during, and after pregnancy (postpartum; PP). sPRR concentrations were measured via ELISA. SBP did not change until third trimester for P PE AGMs (NP PE 120 ± 10 mm Hg; 2nd 132 ± 12 mm Hg; 3rd 155 ± 10 mmHg; 1 Day PP 136 ± 10 mm Hg; p ≤ 0.05). In P PE AGMs, average 3rd trimester fetal length and crown‐to‐rump length following delivery was 16.9 ± 0.6 cm and 16.3 ± 1.0 cm, respectively. Non‐pregnant maternal body weight differed before and after pregnancy (NP PE 3.8 ± 0.1 kg; 1 day PP 4.2 ± 0.1 kg; p ≤ 0.05). Maternal body weight of P PE females was elevated in the 3rd trimester and at 1 day PP (NP PE 3.7 ± 0.1 kg; 3rd trimester 4.8 ± 0.1 kg; 1 day PP 4.3 ± 0.1 kg; p ≤ 0.05). Water intake of AGMs with PE did not differ between pre‐pregnancy and pregnancy (NP PE 168.4 ± 40.9 mL/day; P PE 112 ± 40.9 mL/day; p ≥ 0.05). Urinary excretion rate also did not differ before and during pregnancy for P PE females (NP PE 109.1 ± 27.8 mL/day; P PE 103.5 ± 27.8 mL/day; p ≥ 0.05). Plasma sPRR concentrations increased in PE pregnancy relative to pre‐pregnancy values (NP PE 4966.2 ± 921.5 pg/ml vs. P PE 8250.8 ± 635.9 pg/ml; p ≤ 0.05). Furthermore, urinary protein excretion increased in PE pregnancy (NP PE 300.4 ± 82.3 mg/day vs. P PE 589.7 ± 58.2; p ≤ 0.05). Thus, proteinuria during PE pregnancy in AGMs is associated with increased plasma concentrations of sPRR. Early detection of elevated sPRR and/or proteinuria may be effective markers of the onset of preeclampsia. Continued studies of the association between sPRR and PE will include assessment of renal function and sodium/water balance in NT and PE AGMs, pregnant normotensive (NT) AGM plasma sPRR concentrations, as well as urine and tissue sPRR measurements.Support or Funding InformationChelsea Weaver: American Heart Association Predoctoral Fellowship 17PRE33670127. Frederique Yiannikouris: NIH NHLBI RO1 HL142969‐01.