Expression and localization pattern of ABCA1 in diverse human placental primary cells and tissues

Nikitina, Liudmila; Wenger, F.; Baumann, Marc; Surbek, Daniel; Körner, Meike; Albrecht, Christiane

doi:10.1016/j.placenta.2011.03.003

Cited by 40 publications

(34 citation statements)

References 38 publications

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“…A previous study at term concluded that SRB-1 does not play a critical role in controlling plasma cholesterol concentration, even in pregnant women with high or low levels of cholesterol ( 30 ). Our fi ndings are in agreement with others who have reported a marked ABCA1 expression level in diverse placental cell types ( 31 ), and the presence of LDL-R , LRP-1 , and SRB-1 in placental tissues ( 15 ). However, in contrast to the current data, Wadsack et al showed lower mRNA expression of LDL-R in FGR-S, and Stepan et al ( 32 ) reported higher.…”

Section: Maternal Serum Umbilical Cord Serum and Placental Tissuesupporting

confidence: 93%

Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype

Hentschke

Poli-de-Figueiredo

Costa

et al. 2013

Journal of Lipid Research

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Gestational hyperlipidemia is a common factor in pregnancy in which the maternal circulating lipid profile changes from an anabolic to a catabolic state, increasing lipids, especially triglycerides (TGs) and lipoproteins ( 1 ). From the 12th week of gestation, phospholipids, total cholesterol (TC), LDL, HDL, and TGs increase in response to estrogen stimulation and insulin resistance ( 2 ). Thus, during the fi rst two trimesters, it is common to see maternal fat accumulation; however, in the third trimester there is enhanced lipolytic activity and decreased lipoprotein lipase (LPL) activity in the adipose tissue, consequently, fat storage declines or ceases ( 3 ). Early in gestation, the lipids are required to develop the fetal brain and central nervous system ( 4 ), to build cell membranes, and as a precursor of bile acids and steroid hormones ( 2 ). However, a maternal source of lipids is still required until term, but in lower amounts, possibly due to some fetal-derived lipids Abstract Atherosis of spiral arteries in uteroplacental beds from preeclamptic women resemble those of atherosclerosis, characterized by increased plasma lipids and lipoproteins. We hypothesized that: 1 ) lipoprotein receptors/ transporters in the placenta would be upregulated in preeclampsia, associated with increased maternal and fetal lipoprotein concentrations; and 2 ) expression of these would be reduced in preeclamptic placentae from women delivering small-for-gestational-age (SGA) infants. Placental biopsies and maternal and umbilical serum samples were taken from 27 normotensive and 24 preeclamptic women. Maternal/ umbilical cord serum LDL, HDL, total cholesterol, and triglycerides were measured. Placental mRNA expression of lipoprotein receptors/transporters were quantifi ed using quantitative RT-PCR. Protein localization/expression of LDL receptor-related protein 1 (LRP-1) in the preeclamptic placentae with/without SGA was measured by immunohistochemistry. Placental mRNA expression of all genes except paraoxonase-1 ( PON-1 ), microsomal triglyceride transfer protein ( MTTP ), and protein disulfi de isomerase family A member 2 ( PDIA2 ) were observed. No differences for any lipoprotein receptors/transporters were found between groups; however, in the preeclamptic group placental LRP-1 expression was lower in SGA delivering mothers (n = 7; P = 0.036). LRP-1 protein was localized around fetal vessels and Hofbauer cells. This is the fi rst detailed study of maternal/fetal lipoprotein concentrations and placental lipoprotein receptor mRNA expression in normotensive and preeclamptic pregnancies. These fi ndings do not support a role of altered lipid metabolism in preeclampsia, but may be involved in fetal growth. -Hentschke, M. R., C. E. Abbreviations: AGA, adequate-for-gestational-age; BMI, body mass index; FGR, fetal growth restriction; FGR-M, fetal growth restriction without hemodynamic changes; FGR-S, fetal growth restriction with hemodynamic changes; IQR, interquartile range; LDL-R , LDL receptor; LRP-1, LDL receptor-related pro...

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Section: Maternal Serum Umbilical Cord Serum and Placental Tissuesupporting

confidence: 93%

Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype

Hentschke

Poli-de-Figueiredo

Costa

et al. 2013

Journal of Lipid Research

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“…It was concluded that a regulatory function of ABCA1 in intracellular signalling with regard to cell differentiation and hormone metabolism seems to be operating during pregnancy. 37 In our study, the p.Lys1587 is not a deleterious mutation comparable to ABCA1 gene knockout, but because of its effect on maternal cholesterol levels, we postulate a similar effect in human embryogenesis for p.Lys1587 at least in severe SLOS cases as for ABCA1 knockout in mice.…”

Section: Discussionmentioning

confidence: 51%

“…35,36 A particularly strong support for our conclusion with regard to ABCA1 as a modifier of SLOS severity is that the protein was found to be highly expressed in the placenta. 37 It was shown that ABCA1 is localised in the maternal tissue, namely in the syncytiotrophoblast, especially at the apical maternal facing side as well as at the fetal side (Figure 2). [37][38][39] Here it acts as a regulator of reverse cholesterol transport by interacting with ApoA-I, which transfers cholesterol to HDL as was shown in macrophages.…”

Section: Discussionmentioning

confidence: 98%

“…37 It was shown that ABCA1 is localised in the maternal tissue, namely in the syncytiotrophoblast, especially at the apical maternal facing side as well as at the fetal side (Figure 2). [37][38][39] Here it acts as a regulator of reverse cholesterol transport by interacting with ApoA-I, which transfers cholesterol to HDL as was shown in macrophages. 24 In our study, no association was demonstrated between maternal ABCA1 genotype with regard to the SNP p.Arg1587Lys and the plasma cholesterol measured in the SLOS patients.…”

Section: Discussionmentioning

confidence: 98%

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Maternal ABCA1 genotype is associated with severity of Smith–Lemli–Opitz syndrome and with viability of patients homozygous for null mutations

et al. 2012

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The Smith-Lemli-Opitz syndrome (SLOS [MIM 270400]) is an autosomal recessive malformation syndrome that shows a great variability with regard to severity. SLOS is caused by mutations in the D7sterol-reductase gene (DHCR7), which disrupt cholesterol biosynthesis. Phenotypic variability of the disease is already known to be associated with maternal apolipoprotein E (ApoE) genotype. The aim of this study was to detect additional modifiers of the SLOS phenotype. We examined the association of SLOS severity with variants in the genes for ApoC-III, lecithin-cholesterol acyltransferase, cholesteryl-ester transfer protein, ATP-binding cassette transporter A1 (ABCA1), and methylene tetrahydrofolate reductase. Our study group included 59 SLOS patients, their mothers, and 49 of their fathers. In addition, we investigated whether ApoE and ABCA1 genotypes are associated with the viability of severe SLOS cases (n ¼ 21) caused by two null mutations in the DHCR7 gene. Maternal ABCA1 genotypes show a highly significant correlation with clinical severity in SLOS patients (P ¼ 0.007). The rare maternal p.1587Lys allele in the ABCA1 gene was associated with milder phenotypes. ANOVA analysis demonstrated an association of maternal ABCA1 genotypes with severity scores (logarithmised) of SLOS patients of P ¼ 0.004. Maternal ABCA1 explains 15.4% (R 2 ) of severity of SLOS patients. There was no association between maternal ApoE genotype and survival of the SLOS fetus carrying two null mutations. Regarding ABCA1 p.Arg1587Lys in mothers of latter SLOS cases, a significant deviation from HardyWeinberg equilibrium (HWE) was observed (P ¼ 0.005). ABCA1 is an additional genetic modifier in SLOS. Modifying placental cholesterol transfer pathways may be an approach for prenatal therapy of SLOS.

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“…ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 mediate the efflux of cholesterol across cellular membranes and removes excess cellular cholesterol [29]. The distribution of ABC isoforms in apical or basal localization is controversial [30][31][32]. ABC and SR-B1 seem to be also involved in the cholesterol efflux to fetal lipoproteins [28 & ,33].…”

Section: Cholesterol Placental Transfermentioning

confidence: 99%

Placental regulation of fetal nutrient supply

Larqué

Ruiz-Palacios

Koletzko

2013

Current Opinion in Clinical Nutrition and Metabolic Care

113

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Expression and localization pattern of ABCA1 in diverse human placental primary cells and tissues

Cited by 40 publications

References 38 publications

Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype

Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype

Maternal ABCA1 genotype is associated with severity of Smith–Lemli–Opitz syndrome and with viability of patients homozygous for null mutations

Placental regulation of fetal nutrient supply

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