The Targeting of Nuclear Factor Kappa B by Drugs Adopted for the Prevention and Treatment of Preeclampsia

Abstract

Preeclampsia (PE) is characterised by high levels and activity of the transcription factor Nuclear Factor kappa B (NFĸB) in the maternal blood and placental cells. This factor is responsible for the regulation of over 400 genes known to influence processes related to inflammation, apoptosis and angiogenesis, and cellular responses to oxidative stress and hypoxia. Although high NFĸB activity induces hypoxia and inflammation, which are beneficial for the process of implantation, NFĸB level should be reduced in the later stages of physiological pregnancy to favour maternal immunosuppression and maintain gestation. It is believed that the downregulation of NFĸB activity by pharmacotherapy might be a promising way to treat preeclampsia. Interestingly, many of the drugs adopted for the prevention and treatment of preeclampsia have been found to regulate NFĸB activity. Despite this, further innovation is urgently needed to ensure treatment safety and efficacy. The present article summarizes the current state of knowledge about the drugs recommended by cardiology, obstetrics, and gynaecology societies for the prevention and treatment of preeclampsia with regard to their impact on the cellular regulation of NFĸB pathways.

Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

“…Under physiological conditions, sirtuins regulate the generation of reactive oxygen species by regulating the acylation/deacylation process of antioxidant enzymes such as SOD1 and SOD2 [11,12]. It can also regulate the activation and transplantation of signaling pathways such as NF-κB and AKT through the same mechanism, thereby regulating the production of adenosine triphosphate and infammatory factors, thereby participating in intracellular important physiological processes such as gene transcription, energy metabolism, and antioxidant defense that are important for maintaining the stability of the intracellular environment and normal pregnancy [13]. When the expression of sirtuins is downregulated, their protective efect is also weakened, which can induce abnormalities such as maintenance stress, excessive infammatory response, and energy metabolism disorders, leading to the occurrence of pathological pregnancy such as preeclampsia, GDM, and ICP [14].…”

Placental oxidative stress and monoamine oxidase expression are increased in severe preeclampsia: a pilot study

“…Among the deleterious effects of increased ROS levels is the degradation NFkB inhibitors, preeclampsia being associated with increased NFkB activity which favors the oxidative stress persistence [6]. We have previously demonstrated that induction of endogenous MAOs in murine vascular rings occurred after acute incubation with angiotensin II and lipopolysaccharide via NFkB [40].…”

“…At variance, in preeclampsia, the persistence of increased placental level of NFkB via partially elucidate mechanisms is responsible for the endothelial dysfunction and perpetuation of inflammation and oxidative stress (recently reviewed in ref. [6]).…”

The NFκB Signaling Pathway Is Involved in the Pathophysiological Process of Preeclampsia

“…Aspirin is the drug most commonly used clinically to prevent PE. Aspirin inhibits activation of the NFκB pathway by preventing NFκB nuclear translocation and binding to DNA motif elements or by binding to the IKKα protein as a competitive inhibitor of ATP 44 124 125 . Aspirin prevents redox-sensitive NFκB/miR-155/eNOS axis thereby reversing TNF-α-mediated downregulation of eNOS and endothelial failure 126 .…”

“…Magnesium sulphate is one of the most commonly used drugs in obstetrics and is often used to lower blood pressure, prevent eclampsia and protect fetal nerves. Magnesium sulphate also has an inhibitory effect on the NFκB pathway 124 127 . In animal studies, MgSO 4 was found to protect cranial nerves in PE rats by inhibiting the NFκB/ICAM-1 signaling cascade 128 .…”