Shah Dania A, Khalil Raouf A
Vascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Vascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Biochem Pharmacol. 2015 Jun 15;95(4):211-26. doi: 10.1016/j.bcp.2015.04.012. Epub 2015 Apr 24.
Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca(2+), protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.
子痫前期是一种与妊娠相关的疾病，其特征为高血压，可导致母婴发病和死亡；然而，其中涉及的病理生理机制尚不清楚。诱发的人口统计学、遗传和环境风险因素可导致子宫胎盘细胞活性因子如整合素、基质金属蛋白酶、细胞因子和主要组织相容性复合体分子出现局部异常，从而导致血管重塑减少、子宫胎盘血管收缩、滋养层细胞凋亡以及胎盘发育异常。胎盘形成缺陷和滋养层对子宫肌层的侵袭减少会导致子宫胎盘灌注压（RUPP）降低和胎盘缺血/缺氧，这是子痫前期的一个重要事件。RUPP可刺激循环生物活性因子的释放，如抗血管生成因子可溶性fms样酪氨酸激酶-1和可溶性内皮糖蛋白，这些因子会导致与促血管生成因子血管内皮生长因子和胎盘生长因子失衡，或导致炎性细胞因子、活性氧、缺氧诱导因子-1和AT1血管紧张素受体激动性自身抗体的释放。循环生物活性因子作用于内皮细胞，导致全身性内皮病变、内皮功能障碍、一氧化氮和前列环素等血管舒张剂减少以及内皮素-1和血栓素A2等血管收缩剂增加，从而导致血管收缩增强。这些生物活性因子还刺激血管平滑肌收缩机制，包括Ca(2+)、蛋白激酶C和Rho激酶，并诱导细胞外基质重塑，导致进一步的血管收缩和高血压。虽然目前治疗选择有限，但了解潜在机制有助于设计子痫前期管理的新干预措施。
