Manten G T R, van der Hoek Ytje Y, Marko Sikkema J, Voorbij Hieronymus A M, Hameeteman Ton M, Visser Gerard H A, Franx Arie
Department of Perinatology and Gynaecology, F05.829, University Medical Center, PO Box 85090, 3508 AB Utrecht, The Netherlands.
Med Hypotheses. 2005;64(1):162-9. doi: 10.1016/j.mehy.2004.04.026.
Endothelial cell dysfunction is a key feature of the pathogenesis of pre-eclampsia. The cause of the endothelial cell injury is probably multifactorial, but poor placenta perfusion plays a major role. In pre-eclampsia, characteristic pathological lesions in the placenta are fibrin deposits, acute atherosis and thrombosis. The similarity between the lesions of pre-eclampsia and atherosclerosis has led to speculations of a common pathophysiological pathway. An abnormal lipid profile is known to be strongly associated with atherosclerotic cardiovascular disease and has a direct effect on endothelial function. Abnormal lipid metabolism seems important in the pathogenesis of pre-eclampsia too. An elevated plasma lipoprotein (a) concentration is a known risk factor for atherosclerotic cardiovascular disease. In this paper, we discuss three hypotheses about the mechanisms by which lipoprotein (a) may be associated with pre-eclampsia: 1. Lp(a), as an acute-phase reactant, transporting cholesterol to sites of endothelial damage for reparation, temporarily increases during pregnancy and increases more during a pregnancy complicated by mild to moderate pre-eclampsia as compared to an uncomplicated pregnancy, in response to a greater extend of endothelial injury in pre-eclampsia. After delivery, pre-eclampsia subsides and Lp(a) concentrations return to baseline levels. 2. In cases of severe pre-eclampsia, there is even more extensive endothelial damage and consequently a higher consumption of Lp(a) in reparation of this vascular damage. These women will have lower concentrations of Lp(a). 3. High baseline concentrations of Lp(a), which are genetically determined, may induce or contribute to the development of pre-eclampsia by promoting endothelial dysfunction. In this line of reasoning one would expect to find higher concentrations of Lp(a) in women at risk for developing pre-eclampsia in a future pregnancy or with a history of pre-eclampsia. As discussed above, these women are also at increased risk for future cardiovascular disease as compared to women with a history of normal pregnancy. The pathophysiologic changes associated with cardiovascular disease may also be responsible for the increased incidence of pre-eclampsia in these women.
内皮细胞功能障碍是先兆子痫发病机制的关键特征。内皮细胞损伤的原因可能是多因素的，但胎盘灌注不良起主要作用。在先兆子痫中，胎盘的特征性病理病变是纤维蛋白沉积、急性动脉粥样硬化和血栓形成。先兆子痫与动脉粥样硬化病变之间的相似性引发了对共同病理生理途径的推测。已知异常的血脂谱与动脉粥样硬化性心血管疾病密切相关，并直接影响内皮功能。异常的脂质代谢在先兆子痫的发病机制中似乎也很重要。血浆脂蛋白(a)浓度升高是动脉粥样硬化性心血管疾病的已知危险因素。在本文中，我们讨论了关于脂蛋白(a)可能与先兆子痫相关的机制的三种假说：1. Lp(a)作为一种急性期反应物，将胆固醇转运到内皮损伤部位进行修复，在孕期暂时升高，与未合并先兆子痫的妊娠相比，在合并轻度至中度先兆子痫的妊娠中升高幅度更大，这是对先兆子痫中更广泛的内皮损伤的反应。分娩后，先兆子痫消退，Lp(a)浓度恢复到基线水平。2. 在重度先兆子痫病例中，存在更广泛的内皮损伤，因此在修复这种血管损伤时对Lp(a)的消耗更高。这些女性的Lp(a)浓度会更低。3. 由基因决定的高基线Lp(a)浓度可能通过促进内皮功能障碍诱导或促成先兆子痫的发生。按照这种推理，人们预期在未来妊娠有发生先兆子痫风险或有先兆子痫病史的女性中会发现更高浓度的Lp(a)。如上所述，与有正常妊娠史的女性相比，这些女性未来患心血管疾病的风险也增加。与心血管疾病相关的病理生理变化也可能是这些女性先兆子痫发病率增加的原因。
