Fetal High-Density Lipoproteins: Current Knowledge on Particle Metabolism, Composition and Function in Health and Disease

Figures

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  Figure 1. Described routes how maternal cholesterol is transported across the human placenta. First, maternally derived lipoproteins interact with respective receptors at the microvillous membrane of the syncytium. After uptake of cholesterol in the syncytium, it is secreted/effluxed to lipid-poor acceptor apolipoproteins of fetal HDL. How stroma transfers cholesterol to the fetoplacental endothelium remains elusive. High-density lipoprotein; SR-BI; scavenger receptor BI; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein; LDL-R, low-density lipoprotein receptor; LRP-1, LDL receptor-related protein 1; ABCA1, ATP-binding cassette A1; ABCG1, ATP-binding cassette G1.

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  Figure 2. Schematic representation of differences between adult- and fetal HDL composition and function (indicated with black arrows). Cord blood-derived HDL exhibits several alterations in the apolipoprotein composition, such as decreased levels of apoA-I, apoC-III, apoD, and apoC-II and higher levels of apoE. In the fetus, the activity of CETP is decreased, while the mass and activity of PON1 and the antioxidative capacity are decreased. Fetal HDL is characterized by increased HDL particle size. HDL, high-density lipoprotein; apo, apolipoprotein; PON1, paraoxonase 1; CETP, cholesteryl-ester transfer protein.

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  Figure 3. PE affects maternal and fetal HDL composition and function. Changes are indicated with purple arrows. In maternal HDL, a decrease in PON1 activity, apoM, and S1P content was observed, whereas apoE and LpPLA2 were increased. These changes in HDL composition were associated with reduced anti-inflammatory and anti-oxidative activity, but increased cholesterol efflux capacity. Fetal HDL of PE pregnancies showed similar changes, with reduced PON1 activity and apoM, but increased LpPLA2 and apoE, accompanied by increased cholesterol efflux capacity. Oxidative modifications of lipids were detected in both maternal and fetal HDL. HDL, high-density lipoprotein; apo, apolipoprotein; PON1, paraoxonase 1; LpPLA2, lipoprotein-associated phospholipase A2.

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  Figure 4. GDM affects maternal and fetal HDL composition and function. Changes are indicated with purple arrows. In maternal HDL, a decrease in PON1 activity and mass, apoM, and apoA-I content were observed, whereas SAA and LpPLA2 were increased. These changes in HDL composition were associated with reduced anti-inflammatory and anti-oxidative activity and reduced cholesterol efflux capacity. Fetal GDM-HDL showed the same alterations in PON1 and LpPLA2 activity, apoM and SAA content, and further increased apoE content. GDM was also accompanied by the increased particle size of both maternal and fetal HDL. HDL, high-density lipoprotein; apo, apolipoprotein; PON1, paraoxonase 1; LpPLA2, lipoprotein-associated phospholipase A2; SAA, serum amyloid A.