Cardiovascular and Cerebrovascular Disease Associated microRNAs Are Dysregulated in Placental Tissues Affected with Gestational Hypertension, Preeclampsia and Intrauterine Growth Restriction

Hromadníková, Ilona; Hympánová, Lucie; Krofta, Ladislav

doi:10.1371/journal.pone.0138383

Cited by 116 publications

(97 citation statements)

References 139 publications

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“…miRs-4709-3p, -4717-3p, 4746-3p, -1253, -103a-2-5p) or there were race-specific expression differences (miRs -30c-5p, -20a-5p, -585-5p, -4763-5p). Additionally, we wanted to include miRNAs with known associations to diseases in the vasculature systems (miR-20a-5p, miR-30c-5p, and miR-103a-2-5p)20212223. We also sought to investigate novel miRNAs that have no known targets, as their functionality may be important to hypertension etiology and/or health disparities and have only recently been cataloged by next-generation sequencing (miR-4763-5p, miR-4709-3p, and miR-4717-3p)24.…”

Section: Resultsmentioning

confidence: 99%

Racial differences in microRNA and gene expression in hypertensive women

Dluzen

Hooten

Zhang

et al. 2016

Sci Rep

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Systemic arterial hypertension is an important cause of cardiovascular disease morbidity and mortality. African Americans are disproportionately affected by hypertension, in fact the incidence, prevalence, and severity of hypertension is highest among African American (AA) women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases and we hypothesized that this phenomena may affect health disparities in hypertension. Transcriptional profiling of peripheral blood mononuclear cells from AA or white, normotensive or hypertensive females identified thousands of mRNAs differentially-expressed by race and/or hypertension. Predominant gene expression differences were observed in AA hypertensive females compared to AA normotensives or white hypertensives. Since microRNAs play important roles in regulating gene expression, we profiled global microRNA expression and observed differentially-expressed microRNAs by race and/or hypertension. We identified novel mRNA-microRNA pairs potentially involved in hypertension-related pathways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p. We validated gene expression levels via RT-qPCR and microRNA target validation was performed in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white female hypertensives and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These differences may contribute to the known disparities in hypertension and may be potential targets for intervention.

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Section: Resultsmentioning

confidence: 99%

Racial differences in microRNA and gene expression in hypertensive women

Dluzen

Hooten

Zhang

et al. 2016

Sci Rep

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“…Our finding of expression in HUVECs suggests a role in vascular function which is supported by studies demonstrating miR-126 to be essential for angiogenesis and vascular remodelling under shear stress [29,30] as well effects on vascular endothelial growth factor A (VEGFA) [31] abundance and the production of reactive oxygen species in HUVECs [32]. miR-126 is also expressed in the placenta [33], and found to be decreased in pregnancies complicated by pre-eclampsia and fetal growth retardation [34,35]. …”

Section: Discussionmentioning

confidence: 99%

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

et al. 2016

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We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes. A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycaemic controls. miRNAs were identified using microarray profiling and literature review and validated by quantitative PCR (qPCR). In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, miR-452-5p, miR-126-3p, miR-130b-3p, miR-148a-3p, miR-let-7a-5p and miR-let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase α1 (AMPKα1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKα1 expression was also decreased in placental tissues of IGDM. The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycaemia was very well controlled by current standards. Decreased expression of AMPKα1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at 1 month of age and, if persistent, may predispose offspring to future metabolic disease.

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“…In humans, circulating levels of miR-21 during gestation in the mother positively correlate with evidence of fetal hypoxia [85] and evidence from in vitro studies show the participation of miR-21 in the FGR placental vascular dysfunction [86,87]. By contrast, placental miR-126 levels negatively correlate with the FGR severity [88]. Studies in umbilical endothelium from swine fetuses have shown that the expression of miRNA that targets eNOS and VEGF pathways can be modulated by maternal supplementation with an L-arginine precursor [89].…”

Section: Epigenetics and Endothelial Dysfunctionmentioning

confidence: 99%

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Casanello¹,

Herrera²,

Krause³

2017

Hypoxia and Human Diseases

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Most of the worldwide deaths in patients with non-communicable diseases are due to cardiovascular and metabolic diseases, which are determined by a mix of environmental, genetic and epigenetic factors, and by their interactions. The aetiology of most cardiovascular diseases has been partially linked with in utero adverse conditions that may increase the risk of developing diseases later in life, known as Developmental Origins of Health and Disease (DOHaD). Perinatal hypoxia can program the fetal and postnatal developmental patterns, resulting in permanent modifications of cells, organs and systems function. In spite of the vast evidence obtained from human and animal studies linking development under adverse intrauterine conditions with increased cardiovascular risk, still few is known about the specific effects of intrauterine oxygen deficiency and the related pathogenic mechanisms. Currently, the most accepted processes that program cellular function are epigenetic mechanisms which determine gene expression in a cell-specific fashion. In this chapter we will review the current literature regarding the perinatal exposure to chronic hypoxia and Fetal Growth Restriction (FGR) in humans and animals and how this impinges the cardiovascular physiology through epigenetic, biochemical, morphologic and pathophysiologic modifications that translate into diseases blasting at postnatal life.

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Cardiovascular and Cerebrovascular Disease Associated microRNAs Are Dysregulated in Placental Tissues Affected with Gestational Hypertension, Preeclampsia and Intrauterine Growth Restriction

Cited by 116 publications

References 139 publications

Racial differences in microRNA and gene expression in hypertensive women

Racial differences in microRNA and gene expression in hypertensive women

Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

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