angiotensin-amide and Pre-Eclampsia

Preeclampsia (PE) is a poorly understood pregnancy complication. It has been suggested that changes in the maternal immune system may contribute to PE, but evidence of this remains scarce. Whilst PE is commonly experienced prepartum, it can also occur in the postpartum period (postpartum PE-PPPE), and the mechanisms involved are unknown. Our goal was to determine whether changes occur in the maternal immune system and placenta in pregnancies complicated with PE and PPPE, compared to normal term pregnancies. We prospectively recruited women and collected blood samples to determine the circulating immune profile, by flow cytometry, and assess the circulating levels of inflammatory mediators and angiogenic factors. Placentas were collected for histological analysis. Levels of alarmins in the maternal circulation showed increased uric acid in PE and elevated high-mobility group box 1 in PPPE. Analysis of maternal immune cells revealed distinct profiles in PE vs PPPE. PE had increased percentage of lymphocytes and monocytes whilst PPPE had elevated NK and NK-T cells as well. Elevated numbers of immune cells (CD45+) were detected in placentas from women that developed PPPE, and those were macrophages (CD163+). This work reveals changes within the maternal immune system in both PE and PPPE, and indicate a striking contrast in how this occurs. Importantly, elevated immune cells in the placenta of women with PPPE strongly suggest a prenatal initiation of the pathology. A better understanding of these changes will be beneficial to identify women at high risk of PPPE and to develop novel therapeutic targets.

Topics: Adult; Angiotensin Amide; Case-Control Studies; Female; Humans; Immune System; Inflammation Mediators; Placenta; Postpartum Period; Pre-Eclampsia; Pregnancy; Puerperal Disorders; Quebec; Retrospective Studies; Signal Transduction; Young Adult

To explore the temporal evolution of 25-hydroxyvitamin D [25(OH)D], its epimer, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and minerals in healthy appropriate-for-gestational-age preterms.. A prospective study was undertaken in infants born at 28-32 weeks with monitoring at 1, 3, 5 weeks and term.. Morning plasma and urine calcium; phosphorus; creatinine; PTH, C-terminal and intact FGF23 (iFGF23) and liquid chromatography-tandem mass spectrometry measurements of 25(OH)D were undertaken. Analyses included regression models.. Some 11 infants (5 males) were recruited at a median gestational age of 31.2 weeks (interquartile range: 28.1-31.8). Standard chemistries were normal. No infant was vitamin D deficient; 58% achieved 50 nmol/L with a median intake of 540 IU/day. High concentrations of C-3 epimer were detected. iFGF23 and C-terminal concentrations were persistently elevated (double and ten times adult norms, respectively). Tubular resorption of phosphorus was normal (88%±8%).. Most infants achieved acceptable 25(OH)D3 concentrations. The biologic significance of the elevated FGF23 is unclear.

Topics: Adult; Angiotensin Amide; Biomarkers; Case-Control Studies; Chromatography, Liquid; Diabetes, Gestational; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Pre-Eclampsia; Pregnancy; Prognosis; Prospective Studies; Tandem Mass Spectrometry; Term Birth

Normal pregnancy is associated with refractoriness to the pressor effects of i.v. administered angiotensin II (A II). In pre-eclampsia, this refractoriness to A II is lost several weeks prior to the increase of blood pressure. Infusions of 200 ml of 3% saline or of 40% sorbitol over 30 min, or administration of 2,000 ml of normal saline infused over 2 h, respectively, resulted in an increased vascular angiotensin sensitivity. The effective angiotensin pressor dose (APD) decreased significantly after each test substance (decrease of the mean APD 14.5% after 3% saline, 24% after 40% sorbitol and 25% after normal saline). The data confirm the hypothesis that the principal determinant of pressor responsiveness to A II during pregnancy is arteriolar response; this seems to be modulated by alterations in the sodium content of the vessel wall.

Topics: Adolescent; Adult; Angiotensin Amide; Arterioles; Blood Vessels; Drug Interactions; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Sodium Chloride; Sorbitol

Topics: Angiotensin Amide; Angiotensins; Biological Products; Blood; Female; Humans; Plasma; Pre-Eclampsia; Pregnancy; Rats