Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.

Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist.

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is reduced with preeclampsia and small for gestational aged fetuses.

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is an inhibitory receptor expressed on immune cells. We evaluated LAIR1 in placentas from preeclamptic or small for gestational age (SGA) pregnancies, and placental explant model (1 % O, IL6 and TNFα, or control). LAIR1 mRNA was reduced in placentas from preeclamptic (p < 0.

Trophoblast Side-Population Markers are Dysregulated in Preeclampsia and Fetal Growth Restriction.

Dysregulated progenitor cell populations may contribute to poor placental development and placental insufficiency pathogenesis. Side-population cells possess progenitor properties. Recent human trophoblast side-population isolation identified enrichment of 8 specific genes (CXCL8, ELL2, GATA6, HK2, HLA-DPB1, INTS6, SERPINE3 and UPP1) (Gamage et al.

Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction.

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction.

Investigating ticagrelor in a preclinical pipeline as a novel therapeutic to prevent preterm birth.

In Brief: Preterm birth is the leading cause of perinatal morbidity and mortality, and new therapies that delay preterm birth and improve neonatal outcomes are urgently needed. This study investigates whether ticagrelor inhibits uterine contractility and inflammation in preclinical in vitro, ex vivo (human) and in vivo (mouse) studies, to explore the potential of repurposing ticagrelor for the prevention of preterm birth.

Abstract: Preterm birth remains a significant global health challenge, affecting approximately 10% of pregnancies and resulting in one million deaths globally every year.

The Regulation of Endothelin-1 in Pregnancies Complicated by Gestational Diabetes: Uncovering the Vascular Effects of Insulin.

Gestational diabetes mellitus (GDM) is a condition of pregnancy defined by new-onset hyperglycemia. GDM is associated with impaired maternal endothelial and vascular reactivity. Endothelin-1 (ET-1) is a potent vasoconstrictor that contributes to endothelial dysfunction, however, its abundance and actions in GDM are unclear.

Cell surface associated protein mucin 15 (MUC15) is elevated in preeclampsia.

Background: Mucins are a family of proteins that protect the epithelium. A particular type of mucin, MUC15 is highly expressed in the placenta. This study aimed to characterise MUC15 in preeclampsia and investigate its role in placental stem cell biology.

Paternal Expressed Gene 10 (PEG10) is decreased in early-onset preeclampsia.

Background: Preeclampsia is a severe complication of pregnancy which is attributed to placental dysfunction. The retrotransposon, Paternal Expressed Gene 10 (PEG10) harbours critical placental functions pertaining to placental trophoblast cells. Limited evidence exists on whether PEG10 is involved in preeclampsia pathogenesis.

Quantitative Point of Care Tests for Timely Diagnosis of Early-Onset Preeclampsia with High Sensitivity and Specificity.

Preeclampsia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip-based lateral flow assay (LFA) using lanthanide-doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preeclampsia. We first measured circulating plasma FKBPL and CD44 protein concentrations from individuals with early-onset preeclampsia (EOPE), using ELISA.

Investigating the Effects of Atrial Natriuretic Peptide on the Maternal Endothelium to Determine Potential Implications for Preeclampsia.

Preeclampsia is associated with an increased lifelong risk of cardiovascular disease (CVD). It is not clear whether this is induced by persistent systemic organ and vascular damage following preeclampsia or due to a predisposition to both conditions that share cardiovascular pathophysiology. Common to both CVD and preeclampsia is the dysregulation of corin and its proteolytic product, atrial natriuretic peptide (ANP).

Assessment of the tocolytic nifedipine in preclinical primary models of preterm birth.

Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. Tocolytics are drugs used in cases of imminent preterm birth to inhibit uterine contractions. Nifedipine is a calcium channel blocking agent used to delay threatened spontaneous preterm birth, however, has limited efficacy and lacks preclinical data regarding mechanisms of action.

Circulating Chemerin Is Elevated in Women With Preeclampsia.

Background: Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia.

Sulfasalazine for the treatment of preeclampsia in a nitric oxide synthase antagonist mouse model.

Introduction: Development of a therapeutic that targets the pathophysiological elements of preeclampsia would be a major advance for obstetrics, with potential to save the lives of countless mothers and babies. We recently identified anti-inflammatory drug sulfasalazine as a prospective candidate therapeutic for treatment of preeclampsia. In primary human cells and tissues in vitro, sulfasalazine potently decreased secretion of anti-angiogenic sFlt-1 and sENG, increased production of pro-angiogenic PlGF, mitigated endothelial dysfunction, and promoted whole vessel vasodilation.

SLC38A4 Amino Acid Transporter Expression Is Significantly Lower in Early Preterm Intrauterine Growth Restriction Complicated Placentas.

Intrauterine growth restriction (IUGR), predominantly caused by placental insufficiency, affects partitioning of nutrients to the fetus. The system A sodium-coupled transporters (SNAT or SLC38), of types A1, A2, and A4, control non-essential amino acid uptake and supply. Here, we aimed to investigate the expression of these transporters across different placental disease cohorts and cells.

Hydroxychloroquine reduces soluble Flt-1 secretion from human cytotrophoblast, but does not mitigate markers of endothelial dysfunction in vitro.

Preeclampsia is a multi-system disease that can have severe, even fatal implications for the mother and fetus. Abnormal placentation can lead to ischaemic tissue injury and placental inflammation. In turn, the placenta releases anti-angiogenic factors into the maternal circulation.

Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction.

Placental dysfunction is the leading cause of both preeclampsia and fetal growth restriction. This study aimed to characterize endothelial protein C receptor (EPCR) in preterm preeclampsia, term preeclampsia, and fetal growth restriction (defined by delivery of a small for gestational age [SGA] infant [<10% birthweight centile]) and examine its regulation in primary syncytiotrophoblast. Placental EPCR mRNA and protein were significantly increased in patients with preterm preeclampsia (<34 weeks gestation) compared to gestation-matched controls (p < .

The effect of metformin on cardiovascular markers in female mice consuming a high fat diet.

Background: Metformin, widely used to treat diabetes, is now considered a candidate therapeutic for treatment of cardiovascular disease. This study aimed to assess whether metformin's non-glycaemic effects could mitigate cardiovascular disease indices in female mice consuming a high fat diet (HFD).

Methods: Four-week old female Arc:Arc(S) mice were placed on a standard (std) chow diet or Western-style HFD (22% fat, 0.

Placental galectin-3 is reduced in early-onset preeclampsia.

Preeclampsia is a disease of pregnancy responsible for significant maternal and neonatal mortality. Galectin-3 is a -Galactoside binding protein. This study aimed to characterise galectin-3 in women with preeclampsia and human trophoblast stem cells (hTSCs).

Repurposing existing drugs as a therapeutic approach for the prevention of preterm birth.

In Brief: Preterm birth is the leading cause of perinatal morbidity and mortality; however, current therapies offer limited efficacy to delay birth and improve neonatal outcomes. This review explores the potential of repurposing drugs with known safety profiles to quench uterine contractions and inflammation, identifying promising agents for clinical trials.

Abstract: Preterm birth is the leading cause of neonatal morbidity and mortality globally.

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health.

Preeclampsia affects ∼2-8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health.

Serum Collected from Preeclamptic Pregnancies Drives Vasoconstriction of Human Omental Arteries-A Novel Ex Vivo Model of Preeclampsia for Therapeutic Development.

New-onset maternal hypertension is a hallmark of preeclampsia, driven by widespread endothelial dysfunction and systemic vasoconstriction. Here, we set out to create a new ex vivo model using preeclamptic serum to cause injury to the endothelium, mimicking vascular dysfunction in preeclampsia and offering the potential to evaluate candidate therapeutic interventions. Human omental arteries were collected at caesarean section from normotensive pregnant patients at term (n = 9).

Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction.

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase () in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed.