Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia.
The Obstetrics and Gynecology Clinic Narodni Front "Narodni Front", Kraljice Natalije 62, 11000 Belgrade, Serbia.
Int J Mol Sci. 2023 Jul 12;24(14):11357. doi: 10.3390/ijms241411357.
A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and β-sitosterol) within HDL particles (NCS), the activities of principal modulators of HDL cholesterol's content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG ( < 0.05) and followed by lower levels of cholesterol absorption markers ( < 0.001 for campesterol and < 0.05 for β-sitosterol). Lowering of HDL cholesterol between trimesters in RG ( < 0.05) was accompanied by a decrease in HDL phytosterol content ( < 0.001), apolipoprotein A-I (apoA-I) concentration ( < 0.05), and paraoxonase 1 (PON1) ( < 0.001), lecithin-cholesterol acyltransferase (LCAT) ( < 0.05), and cholesterol ester transfer protein (CETP) activities ( < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCS in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol.
妊娠期间血脂异常的一个特征是高密度脂蛋白(HDL)胆固醇浓度增加,这可能与母体内皮保护有关。然而,子痫前期最常与低 HDL 胆固醇有关,而这种变化的机制尚未得到充分探索。我们旨在研究高危妊娠和晚期子痫前期并发妊娠的 HDL 代谢变化。我们分析了 NCS 中 HDL 颗粒内的胆固醇合成(胆固醇前体:去氢胆固醇、7-脱氢胆固醇和羊毛甾醇)和吸收标志物(植物固醇:菜油固醇和β-谷固醇)、主要调节 HDL 胆固醇含量的活性和主要 HDL 功能蛋白在妊娠中期和晚期的水平。根据妊娠结局,将参与者分为风险组(RG)(70 名妇女)和子痫前期组(PG)(20 名妇女)。与 RG 相比,PG 在妊娠中期的 HDL 胆固醇水平较低(<0.05),随后吸收标志物水平降低(菜油固醇<0.001,β-谷固醇<0.05)。RG 中 HDL 胆固醇在三个时期之间降低(<0.05)伴随着 HDL 植物固醇含量降低(<0.001)、载脂蛋白 A-I(apoA-I)浓度降低(<0.05)、对氧磷酶 1(PON1)降低(<0.001)、卵磷脂胆固醇酰基转移酶(LCAT)降低(<0.05)和胆固醇酯转移蛋白(CETP)活性降低(<0.05)。PG 中没有出现这些纵向变化。晚期子痫前期的发展之前,在妊娠中期会出现较低的 HDL 胆固醇和 NCS。我们提出,肠道 HDL 合成能力降低、LCAT 活性降低和 HDL 介导的胆固醇流出能力受损可能是导致 HDL 胆固醇降低的原因。