Charlton Francesca, Bobek Gabriele, Stait-Gardner Tim, Price William S, Mirabito Colafella Katrina M, Xu Bei, Makris Angela, Rye Kerry-Anne, Hennessy Annemarie
Vascular Immunology Group, The Heart Research Institute, Sydney, New South Wales, Australia.
Lipid Research Group, The Heart Research Institute, Sydney, New South Wales, Australia.
Am J Physiol Regul Integr Comp Physiol. 2017 Jan 1;312(1):R40-R48. doi: 10.1152/ajpregu.00331.2016. Epub 2016 Nov 2.
Preeclampsia is a hypertensive disorder of pregnancy. It is associated with abnormal placentation via poor placental invasion of the uterine vasculature by trophoblast cells, leading to poor placental perfusion, oxidative stress, and inflammation, all of which are implicated in its pathogenesis. A dyslipidemia characterized by low plasma levels of high-density lipoproteins (HDL) and elevated triglycerides has been described in preeclampsia. Apolipoprotein A-I (apoA-I), a constituent of HDL is an anti-inflammatory agent. This study investigated whether apoA-I protects against hypertension and adverse placental changes in a proinflammatory cytokine (TNF-α)-induced model of preeclampsia. Further, this study investigated whether apoA-I protects against the inhibitory effect of TNF-α in a human in vitro model of trophoblast invasion. Administration of apoA-I to pregnant mice before infusion with TNF-α resulted in a significant reduction in the cytokine-induced increase in systolic blood pressure. MRI measurement of T relaxation, a parameter that is tissue specific and sensitive to physiological changes within tissues, showed a reversal of TNF-α-induced placental changes. Preincubation of endothelial cells with apoA-I protected against the TNF-α-induced inhibition of HTR-8/SVneo (trophoblast) cell integration into endothelial (UtMVEC) networks. These data suggest that a healthy lipid profile may affect pregnancy outcomes by priming endothelial cells in preparation for trophoblast invasion.
子痫前期是一种妊娠期高血压疾病。它与胎盘植入异常有关，其原因是滋养层细胞对子宫血管的胎盘侵入不良，导致胎盘灌注不足、氧化应激和炎症，所有这些都与子痫前期的发病机制有关。子痫前期患者存在一种以血浆高密度脂蛋白（HDL）水平降低和甘油三酯升高为特征的血脂异常。载脂蛋白A-I（apoA-I）是HDL的一种成分，是一种抗炎剂。本研究调查了apoA-I是否能在促炎细胞因子（TNF-α）诱导的子痫前期模型中预防高血压和胎盘不良变化。此外，本研究还调查了apoA-I是否能在人滋养层细胞侵袭的体外模型中预防TNF-α的抑制作用。在向怀孕小鼠输注TNF-α之前给予apoA-I，可显著降低细胞因子诱导的收缩压升高。磁共振成像（MRI）测量T弛豫，这是一个组织特异性参数，对组织内的生理变化敏感，结果显示TNF-α诱导的胎盘变化得到逆转。用apoA-I预孵育内皮细胞可预防TNF-α诱导的HTR-8/SVneo（滋养层）细胞整合到内皮（UtMVEC）网络中的抑制作用。这些数据表明，健康的血脂状况可能通过使内皮细胞做好滋养层细胞侵袭的准备来影响妊娠结局。
