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

Abstract

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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