Leiva Andrea, Fuenzalida Bárbara, Westermeier Francisco, Toledo Fernando, Salomón Carlos, Gutiérrez Jaime, Sanhueza Carlos, Pardo Fabián, Sobrevia Luis
Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
Advanced Center for Chronic Diseases (ACCDiS), Faculty of Chemical & Pharmaceutical Sciences and Faculty of Medicine, Universidad de Chile, 8380492 Santiago, Chile ; Faculty of Science, Universidad San Sebastián, 7510157 Santiago, Chile.
Oxid Med Cell Longev. 2015;2015:5346327. doi: 10.1155/2016/5346327. Epub 2015 Nov 30.
Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This condition results in endothelial dysfunction and atherosclerosis in the fetal and placental vasculature. The fetal and placental endothelial dysfunction is related to alterations in the L-arginine/nitric oxide (NO) pathway and the arginase/urea pathway and results in reduced NO production. The level of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), is reduced in nonpregnant women who have hypercholesterolemia, which favors the generation of the superoxide anion rather than NO (from eNOS), causing endothelial dysfunction. However, it is unknown whether MSPH is associated with changes in the level or metabolism of BH4; as a result, eNOS function is not well understood. This review summarizes the available information on the potential link between MSPH and BH4 in causing human fetoplacental vascular endothelial dysfunction, which may be crucial for understanding the deleterious effects of MSPH on fetal growth and development.
孕期会出现母体生理性高胆固醇血症，以确保胎儿正常发育。在某些情况下，母体血浆胆固醇水平会升高至超出这一生理范围，导致母体超生理性高胆固醇血症（MSPH）。这种情况会导致胎儿和胎盘血管系统出现内皮功能障碍和动脉粥样硬化。胎儿和胎盘的内皮功能障碍与L-精氨酸/一氧化氮（NO）途径和精氨酸酶/尿素途径的改变有关，并导致NO生成减少。四氢生物蝶呤（BH4）是内皮型一氧化氮合酶（eNOS）的一种辅助因子，在患有高胆固醇血症的非孕妇中其水平会降低，这有利于超氧阴离子而非（来自eNOS的）NO的生成，从而导致内皮功能障碍。然而，尚不清楚MSPH是否与BH4的水平或代谢变化有关；因此，eNOS的功能尚未得到充分了解。本综述总结了关于MSPH与BH4在导致人类胎儿-胎盘血管内皮功能障碍方面潜在联系的现有信息，这对于理解MSPH对胎儿生长发育的有害影响可能至关重要。
