Preeclampsia is a major complication of pregnancy manifested as hypertension and often intrauterine growth restriction, but the underlying pathophysiological mechanisms are unclear. Predisposing genetic and environmental factors cause placental maladaptations leading to defective placentation, apoptosis of invasive cytotrophoblasts, inadequate expansive remodeling of the spiral arteries, reduced uteroplacental perfusion pressure and placental ischemia. Placental ischemia promotes the release of bioactive factors into the maternal circulation, causing an imbalance between anti-angiogenic soluble fms-like tyrosine kinase-1 and soluble endoglin, and pro-angiogenic vascular endothelial growth factor, placental growth factor and transforming growth factor-β. Placental ischemia also stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin type 1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, causing generalized endotheliosis in systemic, renal, cerebral and hepatic vessels, leading to decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. The bioactive factors also target vascular smooth muscle and enhance the mechanisms of vascular contraction including cytosolic Ca²⁺, protein kinase C and Rho-kinase. The bioactive factors could also target matrix metalloproteinases and the extracellular matrix causing inadequate vascular remodeling, increased arterial stiffening, and further increases in vascular resistance and hypertension. As therapeutic options are limited, understanding the underlying vascular mechanisms and molecular targets should help design new tools for the detection and management of hypertension in pregnancy and preeclampsia.

中文翻译：

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高血压妊娠和先兆子痫的血管机制和分子靶点。

先兆子痫是妊娠的主要并发症，表现为高血压和宫内生长受限，但其潜在的病理生理机制尚不清楚。易感的遗传和环境因素导致胎盘适应不良，导致胎盘缺陷、侵袭性细胞滋养层细胞凋亡、螺旋动脉扩张重建不足、子宫胎盘灌注压降低和胎盘缺血。胎盘缺血促进生物活性因子释放到母体循环中，导致抗血管生成可溶性 fms 样酪氨酸激酶-1 和可溶性内皮糖蛋白与促血管生成血管内皮生长因子、胎盘生长因子和转化生长因子-β 之间的失衡. 胎盘缺血还会刺激促炎细胞因子的释放，缺氧诱导因子、活性氧和血管紧张素 1 型受体激动性自身抗体。这些循环因子以血管内皮为靶点，引起全身、肾、脑和肝血管的广泛内皮增生，导致内皮源性血管扩张剂如一氧化氮、前列环素和超极化因子减少，而血管收缩剂如内皮素-1和血栓素增加A2。生物活性因子还靶向血管平滑肌并增强血管收缩机制，包括细胞溶质 Ca 导致内皮源性血管扩张剂如一氧化氮、前列环素和超极化因子减少，而血管收缩剂如内皮素 1 和血栓素 A2 增加。生物活性因子还靶向血管平滑肌并增强血管收缩机制，包括细胞溶质 Ca 导致内皮源性血管扩张剂如一氧化氮、前列环素和超极化因子减少，而血管收缩剂如内皮素 1 和血栓素 A2 增加。生物活性因子还靶向血管平滑肌并增强血管收缩机制，包括细胞溶质 Ca²⁺，蛋白激酶 C 和 Rho 激酶。生物活性因子还可以靶向基质金属蛋白酶和细胞外基质，导致血管重塑不足、动脉硬化增加，并进一步增加血管阻力和高血压。由于治疗选择有限，了解潜在的血管机制和分子靶点应该有助于设计用于检测和管理妊娠高血压和先兆子痫的新工具。