Maternal serum activin A is not elevated before preeclampsia in women who are at high risk

Blackburn, Catherine; Keelan, Jeffrey A.; Taylor, Rennae S.; North, Robyn A.

doi:10.1067/mob.2003.173

Cited by 12 publications

(7 citation statements)

References 19 publications

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“…Early events such as implantation and development of the placenta are critical for successful pregnancy outcomes[18]. Placental vascular development is tightly regulated by pro-angiogenic angiopoietin 1 (ANG1) and anti-angionetic angiopoietin 2 (ANG2) [19]. During the first trimester, angiogenesis is important for remodeling of uterine spiral arteries into low resistance, high capacity vessels [17,20], which continues until mid-second trimester [19–23].…”

Section: Introductionmentioning

confidence: 99%

“…Placental vascular development is tightly regulated by pro-angiogenic angiopoietin 1 (ANG1) and anti-angionetic angiopoietin 2 (ANG2) [19]. During the first trimester, angiogenesis is important for remodeling of uterine spiral arteries into low resistance, high capacity vessels [17,20], which continues until mid-second trimester [19–23]. Dysfunctional remodeling of uterine spiral arteries is associated with complications of pregnancy, such as preeclampsia[24], gestational diabetes mellitus[25], Intra Uterine Growth Restriction[26], and Small for Gestational Age in the neonate [27].…”

Section: Introductionmentioning

confidence: 99%

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Impact of HIV-1 infection on the IGF-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy

et al. 2019

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Although mother-to-child transmission of HIV has dramatically declined, the number of in utero HIV-exposed, uninfected infants is on the increase. HIV-exposed infants are at an increased risk of mortality, morbidity and slower early growth than their non-HIV exposed counterparts. Maternal HIV increases the risk of having preterm deliveries, intrauterine growth restriction and low birth weight babies. However, the mechanism underlying dysregulation of fetal growth in HIV-infected pregnant women is unknown. We sought to determine whether maternal HIV is associated with dysregulation of the insulin-like growth factor (IGF) axis, some angiogenic factors or other related biomarkers that regulate fetal growth. A total of 102 normotensive pregnant women were enrolled in a small cross-sectional study. Amongst these were thirty-one HIV-1 positive women receiving combination antiretroviral therapy (cART) (Mean age: 30.0 ± 5.1 years; % on ART: 83.9%; median plasma viral load: 683 copies/ml; median CD4 count: 350 cells/ul) and 71 HIV uninfected women (mean age: 27.3 ± 5.8) recruited at delivery. A panel of biomarkers including IGF1 and IGF binding proteins (IGFBP1, IGFBP3), angiopoietins (ANG) 1 and 2, matrix metalloproteinases (MMP) 2 and 9, and galectin 13, was measured in plasma collected from the placental intervillous space. The levels of IGF1, IGFBP1, ANG1, ANG2, MMP2, MMP9 and Gal-13 were not affected by maternal HIV, even when adjusted for maternal factors in linear regression models (all p>0.05). It was observed that HIV-infection in pregnancy did not significantly affect key markers of the IGF axis and angiogenic factors. If anything, it did not affect women. These findings highlight the importance of the use of ART during pregnancy, which maintains factors necessary for fetal development closer to those of healthy women. However, decrease in IGF1 levels might be exacerbated in women con-infected with HIV and malaria.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of HIV-1 infection on the IGF-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy

et al. 2019

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“…When EVT “plugs” are lost during early second trimester, maternal blood flows through the modified vessels to deliver nutrients and oxygen to support fetal growth and development (Pijnenborg et al, 2006a). EVT continue to invade into the myometrium and remodel the SpA until mid-second trimester (Hamilton and Boyd, 1970; Pijnenborg et al, 1983; Blackburn et al, 2003; American Diabetes Association, 2012). The initial steps of uterine spiral artery remodeling consists of vessel dilatation, vascular smooth muscle cells (VSMC) separation, endothelial cell swelling, EVT infiltration, and fibrinoid deposition (Pijnenborg et al, 2006b).…”

Section: Introductionmentioning

confidence: 99%

Extravillous trophoblast cells-derived exosomes promote vascular smooth muscle cell migration

et al. 2014

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Background: Vascular smooth muscle cells (VSMCs) migration is a critical process during human uterine spiral artery (SpA) remodeling and a successful pregnancy. Extravillous trophoblast cells (EVT) interact with VSMC and enhance their migration, however, the mechanisms by which EVT remodel SpA remain to be fully elucidated. We hypothesize that exosomes released from EVT promote VSMC migration.Methods: JEG-3 and HTR-8/SVneo cell lines were used as models for EVT. Cells were cultured at 37°C and humidified under an atmosphere of 5% CO2-balanced N2 to obtain 8% O2. Cell-conditioned media were collected, and exosomes (exo-JEG-3 and exo- HTR-8/SVneo) isolated by differential and buoyant density centrifugation. The effects of exo-EVT on VSMC migration were established using a real-time, live-cell imaging system (Incucyte™). Exosomal proteins where identified by mass spectrometry and submitted to bioinformatic pathway analysis (Ingenuity software).Results: HTR-8/SVneo cells were significantly more (~30%) invasive than JEG-3 cells. HTR-8/SVneo cells released 2.6-fold more exosomes (6.39 × 108 ± 2.5 × 108 particles/106 cells) compared to JEG-3 (2.86 × 108 ± 0.78 × 108 particles/106 cells). VSMC migration was significantly increased in the presence of exo-JEG-3 and exo-HTR-8/SVneo compared to control (−exosomes) (21.83 ± 0.49 h and 15.57 ± 0.32, respectively, vs. control 25.09 ± 0.58 h, p < 0.05). Sonication completely abolished the effect of exosomes on VSMC migration. Finally, mass spectrometry analysis identified unique exosomal proteins for each EVT cell line-derived exosomes.Conclusion: The data obtained in this study are consistent with the hypothesis that the release, content, and bioactivity of exosomes derived from EVT-like cell lines is cell origin-dependent and differentially regulates VSMC migration. Thus, an EVT exosomal signaling pathway may contribute to SpA remodeling by promoting the migration of VSMC out of the vessel walls.

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“…Activin A and inhibin A have also been associated with fetal death and stillbirth 20, with intrauterine growth restriction and preterm delivery without known pre‐eclampsia 21, and with pregnancy‐induced hypertension without proteinuria by some 22, but not by others 8, 9. However, in high‐risk pregnancies activin A and inhibin A were either not elevated or only moderately elevated a few weeks before pre‐eclampsia 11, 13. Furthermore, in other studies of non‐high‐risk pregnancies levels of activin A and inhibin A in women subsequently developing pre‐eclampsia have been comparable to those in women without pre‐eclampsia 21, 23, 24.…”

Section: Discussionmentioning

confidence: 99%

“…In type I diabetes second trimester serum levels of inhibin A were reported close to those in nondiabetic pregnancy 12. In women with chronic hypertension, renal disease, and previous early‐onset pre‐eclampsia, activin A and inhibin A were not or only moderately elevated in pre‐eclampsia 11, 13. In both these studies women with type I diabetes were excluded and the hormones have not been investigated in a population of women with type I diabetes developing pre‐eclampsia.…”

Section: Introductionmentioning

confidence: 90%

Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre‐eclampsia in type I diabetic pregnancies

Ekbom¹,

Damm²,

Andersson

et al. 2006

Acta Obstet Gynecol Scand

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Maternal serum activin A is not elevated before preeclampsia in women who are at high risk

Cited by 12 publications

References 19 publications

Impact of HIV-1 infection on the IGF-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy

Impact of HIV-1 infection on the IGF-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy

Extravillous trophoblast cells-derived exosomes promote vascular smooth muscle cell migration

Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre‐eclampsia in type I diabetic pregnancies

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