Materno-fetal cholesterol transport during pregnancy

Cholesterol is a major nutrient required for fetal growth. It is also a precursor for the synthesis of steroid hormones and essential for the development and maturation of fetal organs. During pregnancy, the placenta controls the transport of cholesterol from the mother to the fetus and vice versa. Cholesterol originating from the maternal circulation has to cross two main membrane barriers to reach the fetal circulation: Firstly, cholesterol is acquired by the apical side of the syncytiotrophoblast (STB) from the maternal circulation as high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)- or very-low-density lipoprotein (VLDL)-cholesterol and secreted at the basal side facing the villous stroma. Secondly, from the villous stroma cholesterol is taken up by the endothelium of the fetal vasculature and transported to the fetal vessels. The proteins involved in the uptake of HDL-, LDL-, VLDL- or unesterified-cholesterol are scavenger receptor type B class 1 (SR-B1), cubulin, megalin, LDL receptor (LDLR) or Niemann–Pick-C1 (NPC1) which are localized at the apical and/or basal side of the STB or at the fetal endothelium. Through interaction with apolipoproteins (e.g. apoA1) cholesterol is effluxed either to the maternal or fetal circulation via the ATP-binding-cassette (ABC)-transporter A1 and ABCG1 localized at the apical/basal side of the STB or the endothelium. In this mini-review, we summarize the transport mechanisms of cholesterol across the human placenta, the expression and localization of proteins involved in the uptake and efflux of cholesterol, and the expression pattern of cholesterol transport proteins in pregnancy pathologies such as pre-eclampsia, gestational diabetes mellitus and intrauterine growth retardation.

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Mutations that affect membrane receptor for LDL are useful for studying normal receptor function

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1982.243.1.e5 ◽

1982 ◽

Vol 243 (1) ◽

pp. E5-E14

Author(s):

R. G. Anderson

Keyword(s):

Cell Biology ◽

Cholesterol Metabolism ◽

Plasma Cholesterol ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Cholesterol Transport ◽

Low Density ◽

Receptor Function ◽

Coated Pits

Low-density lipoprotein (LDL), the major plasma cholesterol transport protein, is taken up by cells through a receptor-mediated process. After internalization through specialized segments of the cell surface called coated pits, the LDL is degraded in the lysosome and the released cholesterol is used by cells to meet various metabolic needs. The discovery of the LDL receptor and the studies of its function have provided new insights into both the biochemical aspects of cholesterol metabolism and the cell biology of receptor-mediated endocytosis. Of paramount importance in all of these studies has been the availability of human cells that express one or more allelic mutations that affect the function of the LDL receptor. These mutations have been valuable for assessing normal receptor function. Just as important, these mutations have been used as a reference point in the development of various cytochemical and biochemical techniques for studying receptor activity.

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Scavenger receptor type B, class 1 (SR-B1) as a receptor for oxidized low density lipoprotein (OxLDL)

Atherosclerosis ◽

10.1016/s0021-9150(00)81357-x ◽

2000 ◽

Vol 151 (1) ◽

pp. 298-299

Author(s):

K. Gillotte-Taylor ◽

A. Boullier ◽

C. Kim ◽

O. Quehenberger ◽

J.L. Witztum ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Receptor Type ◽

Low Density ◽

Type B ◽

Oxidized Low Density Lipoprotein ◽

Class 1

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Thyroid Hormone Reduces Cholesterol via a Non-LDL Receptor-Mediated Pathway

Endocrinology ◽

10.1210/en.2012-1572 ◽

2012 ◽

Vol 153 (11) ◽

pp. 5143-5149 ◽

Cited By ~ 46

Author(s):

Ira J. Goldberg ◽

Li-Shin Huang ◽

Lesley A. Huggins ◽

Shuiqing Yu ◽

Prabhakara R. Nagareddy ◽

...

Keyword(s):

Thyroid Hormone ◽

Knockout Mice ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Low Density ◽

Cholesterol Reduction

Abstract Although studies in vitro and in hypothyroid animals show that thyroid hormone can, under some circumstances, modulate the actions of low-density lipoprotein (LDL) receptors, the mechanisms responsible for thyroid hormone's lipid-lowering effects are not completely understood. We tested whether LDL receptor (LDLR) expression was required for cholesterol reduction by treating control and LDLR-knockout mice with two forms of thyroid hormone T3 and 3,5-diiodo-l-thyronine. High doses of both 3,5-diiodo-l-thyronine and T3 dramatically reduced circulating total and very low-density lipoprotein/LDL cholesterol (∼70%) and were associated with reduced plasma T4 level. The cholesterol reduction was especially evident in the LDLR-knockout mice. Circulating levels of both apolipoprotein B (apo)B48 and apoB100 were decreased. Surprisingly, this reduction was not associated with increased protein or mRNA expression of the hepatic lipoprotein receptors LDLR-related protein 1 or scavenger receptor-B1. Liver production of apoB was markedly reduced, whereas triglyceride production was increased. Thus, thyroid hormones reduce apoB lipoproteins via a non-LDLR pathway that leads to decreased liver apoB production. This suggests that drugs that operate in a similar manner could be a new therapy for patients with genetic defects in the LDLR.

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Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor

Biochemical Journal ◽

10.1042/bj3340009 ◽

1998 ◽

Vol 334 (1) ◽

pp. 9-13 ◽

Cited By ~ 176

Author(s):

Hiroshi YOSHIDA ◽

Nonna KONDRATENKO ◽

Simone GREEN ◽

Daniel STEINBERG ◽

Oswald QUEHENBERGER

Keyword(s):

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Human Monocyte ◽

Binding Activity ◽

Low Density ◽

Blood Monocytes ◽

Oxidized Low Density Lipoprotein

A new receptor for oxidized low-density lipoprotein (LDL), lectin-like oxidized LDL receptor-1 (LOX-1), has recently been cloned from bovine endothelial cells and human lung. A limited tissue-distribution study suggested that the protein was mainly produced by the vascular endothelium. In the present study we demonstrate that LOX-1 is also expressed in macrophages, where it may function as a scavenger receptor. LOX-1 was not detected in undifferentiated THP-1 cells or in freshly isolated human blood monocytes. However, mature human monocyte-derived macrophages and differentiated THP-1 cells showed high levels of LOX-1 transcripts. Consistent with these results, immunofluorescence staining and FACS analysis demonstrated that LOX-1 protein is expressed on the plasma membrane of macrophages. Western-blot analysis of membranes from macrophages (but not those from monocytes) identified a single band, with an apparent molecular mass of about 40 kDa, that displayed oxidized LDL-binding activity. These results suggest that differentiation induces the expression of LOX-1 in macrophages, where it may play a role as a scavenger receptor and/or a receptor for oxidized LDL.

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Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

Biochemical Journal ◽

10.1042/bj2340245 ◽

1986 ◽

Vol 234 (1) ◽

pp. 245-248 ◽

Cited By ~ 31

Author(s):

W Jessup ◽

G Jurgens ◽

J Lang ◽

H Esterbauer ◽

R T Dean

Keyword(s):

Apolipoprotein B ◽

Negative Charge ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Low Density ◽

Lipid Peroxidation Product ◽

Modified Low Density Lipoproteins ◽

Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

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