Department of Nephrology and Hypertension, Meir Medical Center, 44281, Kfar Saba, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Arch Gynecol Obstet. 2018 Aug;298(2):405-413. doi: 10.1007/s00404-018-4824-3. Epub 2018 Jun 25.
To evaluate (a) the properties of high-density lipoproteins (HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1 (PON1), both are negative predictors of cardiovascular risk and (b) HDL function, among women with preeclampsia (PE). PE is a multi-system disorder, characterized by onset of hypertension and proteinuria or other end-organ dysfunction in the second half of pregnancy. Preeclampsia is associated with increased risk for later cardiovascular disease. The inverse association between HDL, cholesterol levels and the risk of developing atherosclerotic cardiovascular disease is well-established.
Twenty-five pregnant women [19 with PE and 6 with normal pregnancy (NP)] were recruited during admission for delivery. HDL was isolated from blood samples. PON1 activity and HDL were analyzed. An in vitro model of endothelial cells was used to evaluate the effect of HDL on the transcription response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) mRNA expression.
PON1 activity (units/ml serum) was lower in the PE group compared to normal pregnancy (NP) (6.51 ± 0.73 vs. 9.98 ± 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared to NP-HDL (3.54 ± 0.72 vs. 0.89 ± 0.35; P = 0.01). PE-HDL exhibited increased VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-α stimulated endothelial cells as compared to NP-HDL.
HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.
评估(a)高密度脂蛋白(HDL)/胆固醇的特性,包括载脂蛋白 A-1(ApoA1)和对氧磷酶 1(PON1),两者都是心血管风险的负预测因子,以及(b)子痫前期(PE)妇女的 HDL 功能。PE 是一种多系统疾病,其特征是在妊娠后半期出现高血压和蛋白尿或其他终末器官功能障碍。PE 与以后发生心血管疾病的风险增加有关。HDL、胆固醇水平与发生动脉粥样硬化性心血管疾病风险之间的负相关关系已得到充分证实。
在分娩期间入院时招募了 25 名孕妇[19 名患有 PE,6 名正常妊娠(NP)]。从血液样本中分离 HDL。分析 PON1 活性和 HDL。使用内皮细胞体外模型评估 HDL 对血管细胞粘附分子-1(VCAM-1)和内皮型一氧化氮合酶(eNOS)mRNA 表达转录反应的影响。
与正常妊娠(NP)相比,PE 组的 PON1 活性(单位/ml 血清)较低(6.51±0.73 与 9.98±0.54;P=0.015)。与 NP-HDL 相比,PE-HDL 释放的 ApoA1 增加(3.54±0.72 与 0.89±0.35;P=0.01)。与 NP-HDL 相比,PE-HDL 刺激 TNF-α 后内皮细胞的 VCAM-1mRNA 表达增加,eNOSmRNA 表达减少。
PE 妇女的 HDL 降低了 PON1 活性并增加了 HDL 颗粒中 ApoA1 的释放。这一过程与 HDL 直径增加有关,提示 HDL 抗氧化活性受损。这些变化可能导致 PE 妇女的长期心血管风险增加。