Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

Abstract

http://hyper.ahajournals.org/ Downloaded from Watanabe et al S(P)RR During Pregnancy 1251invasion and migration. 16,17 Clinically during pregnancy, it is well-known that even women with no complication exhibit BP changes with gestational age; the BP is typically at its lowest between 24 and 26 gestational weeks, increasing thereafter until the end of the pregnancy. 18 In addition, the circulating RAS is involved in the development of hypertensive disorders, including preeclampsia, during pregnancy. 1,16,19 However, no evidence suggests that the tissue RAS contributes to BP changes during pregnancy.On the basis of these background findings, the present study was conducted to examine whether the tissue RAS contributed to BP changes during pregnancy and the incidence of preeclampsia. To this end, we assessed the relationship between plasma s(P)RR concentrations and BP levels during pregnancy in a prospective cohort study. Methods Study ParticipantsIn this prospective cohort study, Japanese pregnant women whose first visit to the National Center for Child Health and Development hospital was at <16 weeks and 0 days of gestation were enrolled between January and December 2010. At recruitment, written informed consent was obtained from all participants. The study protocol was approved by the ethics committee of the National Center for Child Health and Development (Tokyo, Japan).The expected due date was confirmed by ultrasound in all participants. Inclusion criteria were systolic BP <140 mm Hg and diastolic BP <90 mm Hg at the time of enrollment (<16 weeks of gestation) and the absence of preexisting hypertensive disorders and renal disease. The study initially enrolled 477 pregnant women who met the criteria; however, 40 pregnant women were excluded because of early abortion (n=8) or the inability to follow-up because of relocation (n=32), resulting in a total of 437 study participants.Plasma samples were obtained at 3 prenatal visits throughout the pregnancy and at time of delivery. The first sample was obtained before 16 weeks 0 days gestation (early pregnancy), the second between 16 weeks 0 days and 27 weeks 6 days gestation (mid-pregnancy), and the third after 28 weeks 0 days gestation (late pregnancy) at routine blood testing during prenatal visits. The fourth blood sample was obtained at time of delivery. We determined s(P)RR concentrations for first, second, and third trimester using the blood samples obtained in early, middle, and late pregnancy, respectively. We then analyzed s(P) RR concentrations in early pregnancy in association with BP values measured at 16 to 20, 20 to 24, 24 to 28, 28 to 32, 32 to 36, and 36 to 40 weeks of gestation (6 periods). Similarly, s(P)RR concentrations in mid-pregnancy were analyzed in association with BP levels measured at 28 to 32, 32 to 36, and 36 to 40 weeks gestation (3 periods) and s(P)RR concentrations in late pregnancy with BP levels measured at 36 to 40 weeks gestation (1 period). Finally, s(P)RR at delivery was used for analysis of the association between s(P)RR conce...

Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets

“…Furthermore, the mutation of potential furin cleavage sites R275A/KT/R278A can inhibit s(P)RR production [51]. s(P)RR, which binds and activates prorenin, can be regarded as a predictive biomarker of the subsequent high BP during early pregnancy [52]. This evidence suggests that furin-mediated s(P)RR release may be involved in hypertension and the aggravation of atherosclerosis.…”

Water Deprivation Increases (Pro)renin Receptor Levels in the Kidney and Decreases Plasma Concentrations of Soluble (Pro)renin Receptor

“…Plasma concentrations of s(P)RR were elevated in patients with chronic kidney disease (Hamada et al 2013), pregnant women with the development of gestational diabetes mellitus or hypertension later in pregnancy (Watanabe et al 2012(Watanabe et al , 2013, and patients with obstructive sleep apnea syndrome (Nishijima et al 2014(Nishijima et al , 2016.…”

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

“…An sPRR ELISA kit has been developed to detect sPRR in plasma and urine samples (7) . With this assay, increased serum sPRR levels have been demonstrated in patients with heart failure (8), kidney disease (9,10), hypertension (11), and preeclampsia (2). Moreover, serum sPRR is positively associated with serum creatinine, blood urea nitrogen, and urine protein and is inversely associated with the estimated glomerular filtration rate in patients with chronic kidney disease caused by hypertension and type 2 diabetes (9).…”