Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature

Fuenzalida, Bárbara; Sobrevia, Bastián; Cantin, Claudette; Carvajal, Lorena; Salsoso, Rocío; Gutiérrez, Jaime; Contreras-Duarte, Susana; Sobrevía, Luis; Leiva, Andrea

doi:10.1038/s41598-018-25985-6

Cited by 35 publications

(29 citation statements)

References 60 publications

(105 reference statements)

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“…These results show, for first the time, that maternal TC levels have an impact on the feto-placental endothelial dysfunction associated with GDM, although the participating mechanisms remain unknown. We suggest that increased TC levels could worsen feto-placental endothelial function by modifying nitric oxide availability, which has been previously shown in rings from the placental vessels from pregnant women without GDM, but increased TC levels [23][24][25]27]. Therefore, we propose that increased levels of TC, as described in obese women with GDM treated with insulin, could impair feto-placental endothelial function.…”

Section: Discussionsupporting

confidence: 63%

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Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

et al. 2020

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Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.

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Section: Discussionsupporting

confidence: 63%

“…For umbilical vein reactivity assays, normal total cholesterol (NTC) or high total cholesterol (HTC) levels were defined as being over a cut-off point of 280 mg/dL at the term of pregnancy, based on the literature [23,24,27,[52][53][54][55][56].…”

Section: High Cholesterol Cut-off Valuementioning

confidence: 99%

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

et al. 2020

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“…2016-00250). Informed consent and clinical data from patients were obtained as previously described 9 . General maternal (i.e., age, height, weight, blood pressure and glucose levels) and neonatal (i.e., sex, gestational age, weight and height) variables were obtained from the clinical records.…”

Section: Methodsmentioning

confidence: 99%

“…Pregnant women with TC < 280 mg/dL were included in the MPH group, and those with TC ≥ 280 md/dL in the MSPH group. The cut-off value for MSPH reflected values at which human fetoplacental endothelial and vascular dysfunction have been previously reported 1,2,4,5,[7][8][9]24 . The exclusion criteria were maternal obesity at term of pregnancy, pre-gestational and gestational diabetes, preeclampsia, intrauterine growth restriction, foetal malformations and other maternal pathologies as described previously 9 .…”

Section: Methodsmentioning

confidence: 99%

Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia

Fuenzalida

Cantin

Kallol

et al. 2020

Sci Rep

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Maternal physiological (MpH) or supraphysiological hypercholesterolaemia (MSpH) occurs during pregnancy. Cholesterol trafficking from maternal to foetal circulation requires the uptake of maternal LDL and HDL by syncytiotrophoblast and cholesterol efflux from this multinucleated tissue to ApoA-I and HDL. We aimed to determine the effects of MSPH on placental cholesterol trafficking. Placental tissue and primary human trophoblast (pHt) were isolated from pregnant women with total cholesterol <280 md/dL (MPH, n = 27) or ≥280 md/dL (MSPH, n = 28). The lipid profile in umbilical cord blood from MpH and MSpH neonates was similar. the abundance of LDL receptor (LDLR) and HDL receptor (SR-Bi) was comparable between MSpH and MpH placentas. However, LDLR was localized mainly in the syncytiotrophoblast surface and was associated with reduced placental levels of its ligand ApoB. in pHt from MSpH, the uptake of LDL and HDL was lower compared to MpH, without changes in LDLR and reduced levels of SR-BI. Regarding cholesterol efflux, in MSPH placentas, the abundance of cholesterol transporter ABCA1 was increased, while ABCG1 and SR-BI were reduced. In PHT from MSPH, the cholesterol efflux to ApoA-I was increased and to HDL was reduced, along with reduced levels of ABCG1, compared to MPH. Inhibition of SR-BI did not change cholesterol efflux in PHT. The TC content in PHT was comparable in MpH and MSpH cells. However, free cholesterol was increased in MSpH cells. We conclude that MSPH alters the trafficking and content of cholesterol in placental trophoblasts, which could be associated with changes in the placenta-mediated maternal-to-foetal cholesterol trafficking. During the progress of human pregnancy, the concentrations of total cholesterol (TC) and low-(LDL) rises in a physiological (maternal physiological hypercholesterolemia, MPH) 1,2 or supraphysiological (maternal supraphysiological hypercholesterolemia, MSPH) 3,4 way. MSPH is determined in women with TC levels above a cutoff value of 280-300 mg/dL at term of pregnancy or above the 75th percentile for the different trimesters of pregnancy 1-6. Endothelial dysfunction of the macro-and the microvascular vessels of the placenta 4,7-9 as well as development of atherosclerosis in the foetal aorta 1,2,6 has been described in pregnancies with MSPH and increased LDL levels. This information suggest that MSPH could be related to the development of cardiovascular disease in the offspring later in life 2,6,10,11. Despite the increased maternal TC and LDL concentrations, the levels of TC and triglycerides (Tg) of neonates from MSPH pregnancies are comparable to those from MPH pregnancies, suggesting a possible regulation of placental maternal-to-foetal cholesterol trafficking across the placenta 7,12 .

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“…Also, impaired physiological decrease in the uteroplacental vascular resistance in pregnant women FH has been reported [43]. According to a very recent study, maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature [44].…”

Section: Discussionmentioning

confidence: 99%

Gestational hypercholesterolemia helps detect familial hypercholesterolemia and prevent late pregnancy complications

Hyánek¹,

Pehal²,

Dryahina³

et al. 2019

Clin J Obstet Gynaecol

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Introduction: In this retrospective study, we comment on the cause and diagnostic potential of the elevated serum total cholesterol and some non-cholesterol sterols in a population of healthy pregnant women from Prague, Czech Republic. Methods: Based on a total of 21,000 clinical biochemistry tests of healthy pregnant women with hypercholesterolemia observed during pregnancy, a testing group of 84 women with a total cholesterol (TC) above 7.0 mmol/l was established to analyze their non-cholesterol sterols (NCS) by Gas Chromatography-Mass Spectrometry. Lathosterol (Lat) and desmosterol (Des) were evaluated as markers of endogenous cholesterol synthesis, whereas campesterol (Cam) and sitosterol (Sit) were analysed as markers of intestinal absorption. Results: In the basic population, the frequency of gestational hypercholesterolemia with the serum TC levels > 7.0mmol/l was 1 to 136.The mean values were: TC 6.8 mmol/l, LDL-C 4.6 mmol/l, and HDL-C 2.2 mmol/l. In the selected testing group of 84, the mean values were: Lat 7.8+/-1.7 μmol/l, Des 4.7+/-0.9 μmol/l, Cam 9.8+/-2.6 μmol/l, and Sit 9.6+/-3.8 μmol/l. Lat correlated with TC (r = 0.53), LDL-C (r = 0.36), and non-HDL-C (r = 0.35). No such correlations were observed for Cam or Sit. Conclusion: Our fi ndings prove that gestational hypercholesterolemia is caused by increased endogenous cholesterol synthesis via lathosterol. Subsequently, we demonstrate how a single cholesterol test taken in the fi fth to sixth month gestation can effi ciently help detect familial hypercholesterolemia, and prevent related late pregnancy circulatory complications.

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Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature

Cited by 35 publications

References 60 publications

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia

Gestational hypercholesterolemia helps detect familial hypercholesterolemia and prevent late pregnancy complications

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