Hubel C A, Lyall F, Weissfeld L, Gandley R E, Roberts J M
Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
Metabolism. 1998 Oct;47(10):1281-8. doi: 10.1016/s0026-0495(98)90337-7.
The pregnancy disorder preeclampsia is characterized by endothelial cell dysfunction that may be promoted by abnormal increases in circulating lipids, particularly triglycerides and free fatty acids. Serum triglyceride concentration is a major regulatory determinant of low-density lipoprotein (LDL) size and density distribution. Smaller, denser LDL particles have several intrinsic properties capable of inducing endothelial dysfunction. The present nested, case-control study of gestationally matched preeclamptic and normal pregnant women tested the hypothesis that hypertriglyceridemia in preeclampsia is accompanied by decreases in LDL peak particle diameter (predominant LDL size). Plasma LDL peak particle diameter was determined by nondenaturing 2% to 16% polyacrylamide gel electrophoresis. Correlations of LDL diameter with the concentration of serum triglycerides, free fatty acids, total cholesterol, LDL-cholesterol, and apolipoprotein B (apo B) were determined. In the same individuals, we measured serum concentrations of a marker of vascular dysfunction previously reported to be increased in preeclampsia, soluble vascular cell adhesion molecule-1 (VCAM-1), and examined the association of VCAM-1 with LDL diameter and serum lipids. LDL peak particle diameter was decreased in preeclampsia relative to normal pregnancy (P < .01). The LDL-cholesterol:apo B ratio, which frequently decreases with decreasing LDL diameter, was also decreased (P < .04). Triglyceride concentrations were increased in preeclampsia (P < .0002), and there was a significant inverse relationship between LDL peak particle diameter and triglycerides (r = -.55, P < .02). Serum soluble VCAM-1 concentrations were markedly increased in preeclampsia (P < .0003). Apo B (P < .004), free fatty acids (P < .01), total cholesterol (P < .01), and LDL-cholesterol (P < .02) were also increased. VCAM-1 correlated with apo B (r = .50, P < .03) and LDL-cholesterol (r = .50, P < .03), but showed no relationship with the LDL diameter, LDL-cholesterol:apo B ratio, or other lipids. We conclude that the predominance of smaller, denser LDL, a potential contributor to endothelial cell dysfunction, is a feature of preeclampsia. However, the serum VCAM-1 level, one indicator of endothelial involvement, may be influenced more by quantitative lipoprotein changes (serum apo B or LDL-cholesterol) than by LDL particle size.
妊娠疾病子痫前期的特征是内皮细胞功能障碍，循环脂质尤其是甘油三酯和游离脂肪酸的异常增加可能会促进这种功能障碍。血清甘油三酯浓度是低密度脂蛋白（LDL）大小和密度分布的主要调节决定因素。更小、密度更高的LDL颗粒具有几种能够诱导内皮功能障碍的内在特性。本项针对孕周匹配的子痫前期孕妇和正常孕妇的巢式病例对照研究检验了以下假设：子痫前期的高甘油三酯血症伴随着LDL峰值粒径（主要的LDL大小）的减小。通过非变性2%至16%聚丙烯酰胺凝胶电泳测定血浆LDL峰值粒径。确定了LDL直径与血清甘油三酯、游离脂肪酸、总胆固醇、LDL胆固醇和载脂蛋白B（apo B）浓度之间的相关性。在同一批个体中，我们测量了先前报道在子痫前期会升高的血管功能障碍标志物可溶性血管细胞黏附分子-1（VCAM-1）的血清浓度，并研究了VCAM-1与LDL直径和血脂的关联。与正常妊娠相比，子痫前期的LDL峰值粒径减小（P <.01）。经常随着LDL直径减小而降低的LDL胆固醇：apo B比值也降低了（P <.04）。子痫前期患者的甘油三酯浓度升高（P <.0002），且LDL峰值粒径与甘油三酯之间存在显著的负相关（r = -.55，P <.02）。子痫前期患者血清可溶性VCAM-1浓度显著升高（P <.0003）。apo B（P <.004）、游离脂肪酸（P <.01）、总胆固醇（P <.01）和LDL胆固醇（P <.02）也升高。VCAM-1与apo B（r =.50，P <.03）和LDL胆固醇（r =.50，P <.03）相关，但与LDL直径、LDL胆固醇：apo B比值或其他血脂无关联。我们得出结论，更小、密度更高的LDL占优势是子痫前期的一个特征，而LDL是内皮细胞功能障碍的一个潜在促成因素。然而，内皮细胞受累的一个指标血清VCAM-1水平可能更多地受脂蛋白定量变化（血清apo B或LDL胆固醇）的影响，而非LDL颗粒大小的影响。
